SFN, Sulforaphane (mainly Broccoli): Click to Expand ⟱
Features:
Sulforaphane is an isothiocyanate derived from glucoraphanin, a compound found predominantly in cruciferous vegetables such as broccoli, Brussels sprouts, and cabbage. It is well known for its potent antioxidant and detoxification properties and has gained significant attention for its potential chemopreventive and anticancer effects.

Summary
1.primarily attenuates both DNMTs and HDACs, individually suppressing DNA hypermethylation and histones deacetylation, ultimately upregulating NRF2 (best known for NRF2↑)
2.Antioxidant Activity:
• Nrf2 activation leads to the upregulation of a host of antioxidant and detoxification enzymes (e.g., glutathione S-transferase, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1), which in turn decrease oxidative stress and lower ROS levels.
3.Pro-oxidant Effects in Cancer Cells and Under High-Dose Conditions (>=10uM?)
• In certain cancer cell types or at higher concentrations, sulforaphane can paradoxically lead to an increase in ROS levels.
• The elevated ROS may overwhelm the cancer cells’ antioxidant defenses, leading to oxidative stress–mediated cell death (apoptosis).
• This context-dependent pro-oxidant effect has been explored for its potential in selectively targeting cancer cells while leaving normal cells less affected.

- Might not be a good candidate for pro-oxidant strategy depending on concentration >10uM?.
- Strong Activation of Nrf2 (best known for) at low to moderate concentrations, hence reduces oxidative stress in both cancer and normal cells.
- AMPK signaling activated by SFN, high concentrations of ROS are produced
- ROS generation also results in depletion of GSH levels
- HIF-1α and VEGF inhibitor
- Might be effective against cancer stem cells
- But I would not combine that with radiation, as Sulforaphane activates the anti-oxidant master regulator of cells.
- “I very much agree: Sulforaphane is a very good addition, even more when the choice is an anti-oxidant therapy”
- well known as HDAC inhibitor (typically 5-10um concentrations)
-A transient decrease in HDAC activity has also been observed in healthy humans 3 h after providing a daily 200 µM SFN dose, resulting in a plasma concentration of SFN metabolites of 0.1–0.2 µM.


Dose/Bioavailabilty information:
SFN at a daily dose of 2.2 µM/kg body weight, with a mean plasma level of 0.13 µM Sprout 127.6 grams = 205uM±19.9 content yields SFN 0.5 to 2uM in plasma.
However, it is important to consider that at lower doses, specifically 2.5 μM, SFN resulted in a slight increase in cell proliferation by 5.18–11.84% within a 6 to 48 h treatment window.
-A therapeutic dose starts at approx 60 grams of the sprouts.
-100 g of Broccoli sprouts contain about 15–20 mg of sulforaphane
–Organic Broccoli Sprout Powder (Health Ranger) – Avmacol® – NanoPSA (a blend of NanoStilbene™ and Broccoli Sprout Extract).
- -750 mg Sulforaphane Glucosinolate in Daily One Serving (2 capsules) (30mg Sulforaphane)

Total sulforaphane metabolite concentration in plasma was the highest (>2 μM) at 3 h in human subjects who consumed fresh broccoli sprouts (40g)
-human studies with broccoli sprouts or extracts report plasma sulforaphane levels in the low micromolar range (typically 1–2 µM) after ingesting realistic, food-based quantities of sprouts (often in the range of 30–50 g of sprouts or a concentrated extract).

BroccoSprouts are young broccoli sprouts that have garnered attention because they contain high amounts of glucoraphanin—a precursor molecule to sulforaphane. Studies have shown that broccoli sprouts can have sulforaphane precursor levels (i.e., glucoraphanin levels) that are 10 to 100 times higher than those found in mature broccoli heads. Glucoraphanin content in broccoli sprouts can range anywhere from about 30 to over 100 mg per 100 grams of fresh sprouts. Once activated (e.g., during consumption when myrosinase acts on glucoraphanin), these levels translate into a significant sulforaphane yield, meaning that even a small amount of broccoli sprouts can deliver a potent dose of this bioactive compound.

Importantly, glucoraphanin itself is not bioactive. Rather, enzymatic hydrolysis by myrosinase, present in the plant tissue or in the mammalian microbiome, is necessary to form the active component, SFN.
- GFN (glucoraphanin) is hydrolyzed in vivo to SFN via the myrosinase, which is present in gut bacteria as well as the plant itself (also in Radish)
- Do not cook the vegetables, or if you do add myrosinase back in by adding radish.
- mild heat of broccoli (60–70 °C) inactivated ESP and preserved myrosinase and increased SF yield 3–7-fold
- chewing of fresh broccoli sprouts increases the interaction of glucosinolates with myrosinase and consequently, increases the bioavailability of SFN in the body

-Note half-life 2-3 hrs.
BioAv is good (15-80%) but requires myrosinase
Pathways:
- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓(contrary, actually most raises NRF2), TrxR↓**, GSH↓, Catalase↓(contrary), HO1↓(contrary), GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT">DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, Hh↓, GLi↓, GLi1↓, CD133↓, β-catenin↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, 5↓, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells


Scientific Papers found: Click to Expand⟱
1433- Ash,  SFN,    A Novel Combination of Withaferin A and Sulforaphane Inhibits Epigenetic Machinery, Cellular Viability and Induces Apoptosis of Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
eff↑, synergistic inhibition of cellular viability in MCF-7
Bcl-2↓,
BAX↑,
tumCV↓,
DNMT1↓,
DNMT3A↓, DNMT3A and DNMT3B mRNA expression is down-regulated
HDAC↓, significant decreases in HDAC activity

3175- Ash,  SFN,    Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7
DNMTs↓, Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyl transferase (DNMT) inhibitor,
HDAC↓, sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor
eff↑, SFN + WA synergistically promote breast cancer cell death

2703- BBR,  CUR,  SFN,  UA,  GamB  Naturally occurring anti-cancer agents targeting EZH2
- Review, Var, NA
EZH2↓, In fact, several natural products such as curcumin, triptolide, ursolic acid, sulforaphane, davidiin, tanshindiols, gambogic acid, berberine and Alcea rosea have been shown to serve as EZH2 modulators.

1473- BCA,  SFN,    An Insight on Synergistic Anti-cancer Efficacy of Biochanin A and Sulforaphane Combination Against Breast Cancer
- in-vitro, BC, MCF-7
eff↑, cytotoxicity of BCA and SFN was found to be around 24.5 µM and 27.2 µM respectively, while the combination of BCA and SFN had shown an inhibitory activity at about 20.1 µM.
ROS↑,
other↑, profound increase in apoptogenic activity of compounds when treated in combination at lower dose.
ERK↓,
Apoptosis↑,

162- CUR,  EGCG,  SFN,    Shattering the underpinnings of neoplastic architecture in LNCap: synergistic potential of nutraceuticals in dampening PDGFR/EGFR signaling and cellular proliferation
- in-vitro, Pca, LNCaP
p‑PDGF↓, phosphorylation

2163- dietP,  SFN,    Intake of Cruciferous Vegetables Modifies Bladder Cancer Survival
- Human, Bladder, NA
OS↑, a strong and significant inverse association was observed between bladder cancer mortality and broccoli intake
OS∅, There were no significant associations for total vegetables, total fruits, or other individual cruciferous vegetables.

2165- dietP,  SFN,    Broccoli sprout supplementation in patients with advanced pancreatic cancer is difficult despite positive effects—results from the POUDER pilot study
- Trial, PC, NA
Dose↝, Fifteen capsules with pulverized broccoli sprouts containing 90 mg/508 μmol sulforaphane and 180 mg/411 μmol glucoraphanin or methylcellulose were administered daily for up to 1 year.
OS↑, Compared to those of the placebo group, the mean death rate was lower in the treatment group during the first 6 months after intake
eff↝, broccoli sprouts sometimes increased digestive problems, nausea and emesis.

685- EGCG,  CUR,  SFN,  RES,  GEN  The “Big Five” Phytochemicals Targeting Cancer Stem Cells: Curcumin, EGCG, Sulforaphane, Resveratrol and Genistein
- Analysis, NA, NA
Bcl-2↓,
survivin↓,
XIAP↓,
EMT↓,
Apoptosis↑,
Nanog↓,
cMyc↓,
OCT4↓,
Snail↓,
Slug↓,
Zeb1↓,
TCF↓,

1435- GEN,  SFN,    The Effects of Combinatorial Genistein and Sulforaphane in Breast Tumor Inhibition: Role in Epigenetic Regulation
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7
DNMTs↓, GEN extensively studied for its role as DNA methyltransferase (DNMT) inhibitor
HDAC↓, SFN), is known as a histone deacetylase (HDAC) inhibitor
eff↑, Our results indicate that the combination of GEN and SFN is much more effective than their single doses in increasing the rate of apoptosis
TumCCA↑, G2 phase in MDA-MB-231 and G1 phase in MCF-7
HMTs↓, histone methyltransferase (HMT) inhibitor
HDAC2↓, combination downregulates the levels of HDAC2 and HDAC3 both at the mRNA and protein levels
HDAC3↓,
KLF4↓, potential to downregulate KLF4 levels, which plays an important role in stem cell formation.
hTERT↓,

911- QC,  SFN,    Pilot study evaluating broccoli sprouts in advanced pancreatic cancer (POUDER trial) - study protocol for a randomized controlled trial
TumCG↓,
Risk↓, decreased risk of extra-prostatic manifestation of prostate cancer: cruciferous vegetables, in particular broccoli which is rich in sulforaphane and quercetin

2403- SFN,    Reversal of the Warburg phenomenon in chemoprevention of prostate cancer by sulforaphane
- in-vitro, Pca, LNCaP - in-vitro, Pca, 22Rv1 - in-vitro, Pca, PC3 - in-vivo, NA, NA
ECAR↓, SFN treatment: (i) decreased real-time extracellular acidification rate in LNCaP, but not in PC-3 cell line;
HK2↓, (ii) significantly downregulated expression of hexokinase II (HKII), pyruvate kinase M2 and/or lactate dehydrogenase A (LDHA) in vitro in cells and in vivo . HKII: 32%
PKM2↓, PKM2: 45%
LDHA↓, LDHA: 33%
Glycolysis↓, (iii) significantly suppressed glycolysis in prostate of Hi-Myc mice
Warburg↓, Reversal of the Warburg phenomenon

2164- SFN,  dietP,    Broccoli Sprouts Delay Prostate Cancer Formation and Decrease Prostate Cancer Severity with a Concurrent Decrease in HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice
- in-vitro, Pca, NA
HDAC↓, broccoli sprouts, inhibits epigenetic regulators such as histone deacetylase (HDAC) enzymes. significant decline in HDAC3 protein expression in the epithelial cells of prostate ventral
Dose↝, TRAMP mice were fed a 15% broccoli sprout
Risk↓, Broccoli sprouts reduced prostate cancer incidence and progression to invasive cancer by 11- and 2.4-fold at 12 and 28 wk of age, respectively.
TumCP↓,
H3↓, Broccoli sprout consumption also decreased histone H3 lysine 9 trimethylation in the ventral lobe (age 12 wk), and decreased histone H3 lysine 18 acetylation in all prostate lobes (age 28 wk).

2166- SFN,    Sulforaphane targets cancer stemness and tumor initiating properties in oral squamous cell carcinomas via miR-200c induction
- in-vitro, Oral, NA - in-vivo, NA, NA
CSCs↓, sulforaphane dose-dependently eliminated the proliferation rate of OSCC-CSCs
selectivity↑, whereas the inhibition on SG(normal) cells proliferation was limited.
TumCMig↓, sulforaphane treatment of OSCC-CSCs decreased the migration, invasion, clonogenicity, and in vivo tumorigenicity of xenograghts.
TumCI↓,

2167- SFN,    The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice
- in-vitro, PC, MIA PaCa-2 - in-vitro, PC, PANC1
Casp8↑, activation of caspase-8, loss of mitochondrial membrane potential, and loss of plasma membrane integrity
MMP↓,
Casp3↑, Incubations at higher sulforaphane doses (>10 micromol/L) resulted in cleavage of caspase-3 in the G(1) subpopulation, suggesting that the induction of apoptosis
Apoptosis↑,
GSH↓, PANC-1, was positively correlated with a decrease in cellular glutathione levels,
GSH↑, whereas sustained increases in glutathione observed in MIA PaCa-2 cells

2168- SFN,    Amelioration of Alzheimer's disease by neuroprotective effect of sulforaphane in animal model
- in-vivo, AD, NA
*NRF2↑, previously been found to stimulate the Nrf2-ARE pathway
*cognitive↑, ameliorated cognitive function of Aβ-induced AD acute mouse models
other↓, inhibition of Aβ aggregation

1734- SFN,    Sulforaphane Inhibits Nonmuscle Invasive Bladder Cancer Cells Proliferation through Suppression of HIF-1α-Mediated Glycolysis in Hypoxia
- in-vitro, Bladder, RT112
selectivity↑, sulforaphane, a natural chemical which was abundant in cruciferous vegetables, could suppress bladder cancer cells proliferation in hypoxia significantly stronger than in normoxia
TumCP↓,
Glycolysis↓, sulforaphane decreased glycolytic metabolism in a hypoxia microenvironment by downregulating hypoxia-induced HIF-1α and blocking HIF-1α t
Hif1a↓,

2404- SFN,    Prostate cancer chemoprevention by sulforaphane in a preclinical mouse model is associated with inhibition of fatty acid metabolism
- in-vitro, Pca, LNCaP - in-vitro, Pca, 22Rv1 - in-vivo, NA, NA
ACC1↓, SFN (5 and 10 μM) resulted in downregulation of protein and mRNA levels of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN), but not ATP citrate lyase
FASN↓,
CPT1A↓, SFN decreased ACC1, FASN and CPT1A expression in LNCaP and 22Rv1 cells
β-oxidation↓, SFN treatment decreased expression of β-oxidation dehydrogenases
SREBP1?, SFN treatment decreased SREBP1 protein level in prostate cancer cells
HK2↓, Similarly, when Hi-Myc mice were given 1 mg/mouse of sulforaphane three times each week for 5–10 weeks, expression of HKII, PKM2 and LDHA was significantly decreased.
PKM2↓,
LDHA↓,
Glycolysis↓, These results provide evidence that sulforaphane suppresses in vivo glycolysis in prostate cancer cells

2405- SFN,    Sulforaphane Targets the TBX15/KIF2C Pathway to Repress Glycolysis and Cell Proliferation in Gastric Carcinoma Cells
- in-vitro, GC, SGC-7901 - in-vitro, GC, BGC-823
TumCP↓, Sulforaphane can reduce cell proliferation and PKM2-mediated glycolysis in gastric carcinoma cells, apparently by activating the TBX15/KIF2C pathway.
Glycolysis↓,
TBX15↑,
GlucoseCon↓, Overexpressing TBX15 in SGC7901 and BGC823 cells significantly reduced glucose uptake, lactate production, cell viability, expression of KIF2C, and pyruvate kinase M2-mediated (PKM2) glycolysis. These effects were recapitulated by treatment with sulf
lactateProd↓,
tumCV↓,
PKM2↓,
KIF2C↓,

2406- SFN,    Sulforaphane and Its Protective Role in Prostate Cancer: A Mechanistic Approach
- Review, Pca, NA
HK2↓, When TRAMP mice were given 6 μmol/mouse (1 mg/mouse) three times a week for 17–19 weeks, the prostate tumor expression of glycolysis-promoting enzymes such as (HKII), 2 (PKM2) and (LDHA) was decreased by 32–45%
PKM2↓,
LDHA↓,
Glycolysis↓, These results provide evidence that sulforaphane suppresses in vivo glycolysis in prostate cancer cells
LAMP2↑, The study shows that 10–20 μM of sulforaphane significantly increased lysosome-associated membrane protein 2 (LAMP2) in the cell lines
Hif1a↓, sulforaphane has been shown to suppress HIF-1α
DNAdam↓, SFN causes DNA damage and prevents DNA repair in prostate cancer cell
DNArepair↓,
Dose↝, 5 to 100 mg/kg of sulforaphane reduce tumors in animal models [ 5 , 19]. For a 70 kg human, this translates to 350–7000 mg/kg, which is significantly above the upper threshold of tolerable doses

2444- SFN,    Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage
- in-vitro, Nor, MRC-5
*GlucoseCon↓, SFN delayed senescence by decreasing glucose metabolism on the approach to senescence, exhibiting a caloric restriction mimetic-like activity
*ROS↓, and thereby decreased oxidative damage to cell protein and DNA
*Trx↓, This was associated with increased expression of thioredoxin-interacting protein, curbing entry of glucose into cells;
*HK2↓, decreased hexokinase-2
*NRF2↑, SFN is an activator of transcription factor Nrf2 [14] which regulates antioxidant response element- (ARE-) linked gene expression.
*Catalase↓, CAT, PDRX1, and GCLM, expression was increased in senescence and treatment with SFN increased the expression further
*TXNIP↑, increased expression of TXNIP, curbing the entry of glucose into cells
*PFKFB2↓, decreased PFKFB2 and increased G6PD, downregulating glycolysis.
*G6PD↑,

2445- SFN,    Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, SkBr3
TumCCA↑, SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence
P21↑,
p27↑,
NO↑, effects were accompanied by nitro-oxidative stress, genotoxicity and diminished AKT signaling
Akt↓,
ATP↓, decreased pools of ATP and AMPK activation, and autophagy induction
AMPK↑,
TumAuto↑,
DNMT1↓, decreased levels of DNA methyltransferases (DNMT1, DNMT3B)
HK2↓, A decrease in HK2 levels was observed in SFN-treated MDA-MB-231 cells
PKM2↓, and a decrease in PKM2 levels was noticed in SFN-treated MDA-MB-231 and SK-BR-3 cells
HDAC3↓, . In contrast, HDAC3 , HDAC4 , HDAC6 , HDAC7 , HDAC8 ), HDAC9 and HDAC10 (histone deacetylase 10) mRNA levels were decreased in SFN-treated MDA-MB-231 cells
HDAC4↓,
HDAC8↓,

2446- SFN,  CAP,    The Molecular Effects of Sulforaphane and Capsaicin on Metabolism upon Androgen and Tip60 Activation of Androgen Receptor
- in-vitro, Pca, LNCaP
AR↓, Sulforaphane and capsaicin decreased nuclear AR, prostate specific antigen and Bcl-XL levels, and cell proliferation induced by androgen and Tip60 in LNCaP cells.
Bcl-xL↓,
TumCP↓,
Glycolysis↓, Sulforaphane at 10 µM reduced the glycolysis and glycolytic capacity by 42% and 39%,
HK2↓, These bioactive compounds prevented the increase in glycolysis, hexokinase and pyruvate kinase activity, and reduced HIF-1α stabilization induced by androgen and Tip60 in LNCaP cells.
PKA↓,
Hif1a↓, Sulforaphane and Capsaicin Reduced the Increased HIF-1α Levels Induced by Androgen Stimulus and Tip60 Overexpression
PSA↓, Sulforaphane and capsaicin prevented the activation of AR signaling (decreased nuclear AR levels and PSA levels)
ECAR↓, and glycolysis (decreased EACR; and HK and PK activities) induced by androgen and Tip60.
BioAv↑, increased sulforaphane bioavailability can be attained after the intake of sulforaphane-enriched broccoli sprout preparation (generated by quick steaming followed by myrosinase treatment) in mice
BioAv↓, Liposomal and methoxypoly (ethylene glycol)-poly(ε-caprolactone) microencapsulation increase capsaicin bioavailability by 3.34-fold and 6-fold respectively in rats
*toxicity↓, considering that the minimum lethal oral dose of capsaicin is 100 mg/Kg body weight in mice, its consumption could be safely increased

1736- SFN,    Antitumor and antimetastatic effects of dietary sulforaphane in a triple-negative breast cancer models
- in-vitro, BC, NA - in-vivo, BC, NA
TumCG↓, in vivo experiment showed up to 31% tumor growth inhibition after sulforaphane treatment
selectivity↓, The in vitro study confirmed that SFN inhibited cell migration, but only in cells derived from 3D spheroids, not from 2D in vitro cultures.

1735- SFN,    Activation of multiple molecular mechanisms for apoptosis in human malignant glioblastoma T98G and U87MG cells treated with sulforaphane
- in-vitro, GBM, T98G - in-vitro, GBM, U87MG
Apoptosis↑, confirmed apoptosis in glioblastoma cells treated with sulforaphane
Ca+2↑, Increase in intracellular free Ca2+ was detected by fura-2 assay, suggesting activation of Ca2+-dependent pathways for apoptosis.
Bax:Bcl2↑, increased Bax:Bcl-2 ratio
cal2↑, Upregulation of calpain, a Ca2+-dependent cysteine protease, activated caspase-12 that in turn caused activation of caspase-9.
Casp12↑,
Casp9↑,
Cyt‑c↑, cytochrome c was released from mitochondria to cytosol

2552- SFN,  Chemo,    Chemopreventive activity of sulforaphane
- Review, Var, NA
chemoP↑, chemopreventive activity of SFN
TumCG↓, SFN can inhibit the initiation of tumor development or halt the progression of cancer
*ROS↓, SFN can also exhibit chemopreventive behavior by interfering with various signaling pathways that regulate oxidative stress, inflammation, cell proliferation, differentiation, and apoptosis
*Inflam↓,
*Dose↝, In rats, the pharmacokinetics of SFN was assessed following an oral dose of 50 μmol of SFN. The plasma concentration of SFN can be detected at 1 hour and it peaks at 20 μM at 4 hours.
*NRF2↑, epigenetic reactivation of Nrf2 and subsequent induction of downstream target genes HO-1, NQO1, and UGT1A1
*HO-1↑,
*NQO1↑,
NF-kB↓, inactivation of NF-κB is an important chemopreventive mechanism of SFN
ROS↑, It was demonstrated that SFN-induced apoptosis is mediated by reactive oxygen species (ROS)-mediated activation of AMPK in human gastric cancer cells.

1733- SFN,    Sonic Hedgehog Signaling Inhibition Provides Opportunities for Targeted Therapy by Sulforaphane in Regulating Pancreatic Cancer Stem Cell Self-Renewal
- in-vitro, PC, PanCSC - in-vitro, Nor, HPNE - in-vitro, Nor, HNPSC
CSCs↓, In an in vitro model, human pancreatic CSCs derived spheres were significantly inhibited on treatment with SFN
Shh↓, SFN inhibited the components of Shh pathway and Gli transcriptional activity
Gli↓,
Nanog↓, suppressing the expression of pluripotency maintaining factors (Nanog and Oct-4) as well as PDGFRα and Cyclin D1
OCT4↓,
PDGFRA↓,
cycD1↑,
Apoptosis↑, SFN induced apoptosis by inhibition of BCL-2 and activation of caspases
Casp↑,
Smo↓, SFN inhibited the expression of Smo, Gli1 and Gli2.
Gli1↓,
GLI2↓,
Bcl-2↓, SFN induced apoptosis in pancreatic CSCs by inhibiting Bcl-2 expression and through the activation of caspase 3/7
Casp3↑,
Casp7↑,

1732- SFN,    Sulforaphane, a Dietary Component of Broccoli/Broccoli Sprouts, Inhibits Breast Cancer Stem Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, SUM159 - in-vivo, NA, NA
TumCD↑, reduced the size and number of primary mammospheres by 8~125-fold and 45%~75% (P < 0.01), respectively.
CSCs↓, Sulforaphane eliminated breast CSCs in vivo,
Wnt↓, Sulforaphane inhibits breast CSCs and down-regulates Wnt/β-catenin self-renewal pathway
β-catenin/ZEB1↓,
*BioAv↑, Sulforaphane was found to be converted from glucoraphanin, a major glucosinolate in broccoli/broccoli sprouts
angioG↓, Sulforaphane was also shown to suppress angiogenesis and metastasis by down-regulating VEGF, HIF-1α, MMP-2 and MMP-9 (4).
VEGF↓,
Hif1a↓,
MMP2↓,
MMP9↓,
Casp3↑,
*Half-Life∅, Plasma concentrations of sulforaphane equivalents peaked 0.94~2.27 μM in humans 1 hr after a single dose of 200 μmol broccoli sprout isothiocyanates (mainly sulforaphane)

1731- SFN,    Targeting cancer stem cells with sulforaphane, a dietary component from broccoli and broccoli sprouts
- Review, Var, NA
CSCs↓, A number of studies have indicated that sulforaphane may target CSCs
ChemoSen↑, Combination therapy with sulforaphane and chemotherapy in preclinical settings has shown promising results.
NF-kB↓, downregulation of NF-kB activity by sulforaphane
Shh↓, Inhibits SHH pathway (Smo, Gli1, Gli2)
Smo↓,
Gli1↓,
GLI2↓,
PI3K↓, Inhibits PI3K/AKT pathway
Wnt↓, Inhibits Wnt/b-catenin pathway
β-catenin/ZEB1↓,
Nanog↓, sulforaphane was found to reduce the expression of SHH pathway components, as well as downstream target genes (e.g.,Nanog, Oct-4, VEGF and ZEB-1)
COX2↓, han et al. suggested that sulforaphane inhibited the EMT process via the COX-2/MMP2,9/ZEB1, Snail and miR-200c/ZEB1 pathways,
Zeb1↓,
Snail↓,
ChemoSideEff↓, More importantly, the combination therapy abolished tumor-initiating potential in vivo, without inducing additional side effects
eff↑, Broccoli sprouts contain approximately 20-times more glucoraphanin than broccoli, which represents typically 74% of all glucosinolates in the sprouts
*BioAv↑, Again, the bioavailability of sulforaphane from broccoli sprouts or broccoli sprout preparations heavily relies on the presence of plant myrosinase.

1730- SFN,    Sulforaphane: An emergent anti-cancer stem cell agent
- Review, Var, NA
BioAv↓, When exposed to high temperatures during meal preparation, myrosinase can be degraded, lose its function, and subsequently compromise the synthesis of SFN.
BioAv↑, eating raw cruciferous vegetables, instead of heating them can significantly improve the biodisponibility of SFN and its subsequent beneficial effects.
GSTA1↑, induction of Phase II enzymes [glutathione S-transferase (GST)
P450↓, (cytochrome P450, CYP) inhibition
TumCCA↑, herb-derived agent can also promote cell cycle arrest and apoptosis by regulating different signaling pathways including Nuclear Factor erythroid Related Factor 2 (Nrf2)-Keap1 and NF-κB.
HDAC↓, modulate the activity of some epigenetic factors, such as histone deacetylases (HDAC),
P21↑, upregulation of p21 and p27,
p27↑,
DNMT1↓, SFN was able to decrease the expression of DNMT1 and DNMT3 in LnCap prostate cancer cells
DNMT3A↓,
cycD1↑, reduce methylation in Cyclin D2 promoter, thus inducing Cyclin D2 gene expression in those cells
DNAdam↑, SFN induced DNA damage, enhanced Bax expression and the release of cytochrome C followed by apoptosis
BAX↑,
Cyt‑c↑,
Apoptosis↑,
ROS↑, SFN increased reactive oxygen species (ROS), apoptosis-inducing factor (AIF)
AIF↑,
CDK1↑,
Casp3↑, activation of caspase-3, -8, and -9
Casp8↑,
Casp9↑,
NRF2↑, SFN significantly activated the major antioxidant marker Nrf2 and decreased NFκB, TNF-α, IL-1β
NF-kB↓,
TNF-α↓,
IL1β↓,
CSCs↓, SFN, have attracted attention due to their anti-CSC effect
CD133↓,
CD44↓,
ALDH↓,
Nanog↓,
OCT4↓,
hTERT↓,
MMP2↓,
EMT↓, SFN was reported to inhibit EMT and metastasis in the NSCLC, the cell lines H1299
ALDH1A1↓, ALDH1A1), Wnt3, and Notch4, other CSC-related genes inhibited by SFN treatment
Wnt↓,
NOTCH↓, SFN can inhibit aberrantly activated embryonic pathways in CSCs, including Sonic Hedgehog (SHH), Wnt/β-catenin, Cripto-1 (CR-1), and Notch.
ChemoSen↑, These results suggest that the antioxidant properties of SFN do not impact the cytotoxicity of antineoplastic drugs, but on the contrary, seems to improve it.
*Ki-67↓, Ki-67 and HDAC3 levels significantly decreased in benign breast tissues, and there was also a reduction in HDAC activity in blood cells
*HDAC3↓,
*HDAC↓,

1729- SFN,    Discovery and development of sulforaphane as a cancer chemopreventive phytochemical
- Review, Nor, NA
eff↑, but mild heating of broccoli (60–70 °C) inactivated ESP and preserved myrosinase and increased SF yield 3–7-fold
angioG↓,
VEGF↓,
MMP9↓,
MMP2↓,

1728- SFN,    Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens
- Review, Nor, NA
eff↑, 3-day-old sprouts of cultivars of certain crucifers including broccoli and cauliflower contain 10-100 times higher levels of glucoraphanin.All sprouts were grown with a 16-h light and 8-h dark photoperiod and a corresponding 25/20°C cycle for agar-gr
eff↓, The generally lower potencies of frozen broccoli samples may have been due to unfavorable storage conditions or to removal of glucosinolates during the blanching process

1727- SFN,    Glucoraphanin, sulforaphane and myrosinase activity in germinating broccoli sprouts as affected by growth temperature and plant organs
- Analysis, Nor, NA
eff↑, Sulforaphane formation was highest in cotyledon and lowest in root. Sprouts grown at 25 °C had higher glucoraphanin content
eff↓, Glucoraphanin content and sulforaphane formation declined with sprouts growth.

1726- SFN,    Sulforaphane: A Broccoli Bioactive Phytocompound with Cancer Preventive Potential
- Review, Var, NA
Dose↝, Most clinical trials utilize doses of GFN ranging from 25 to 800 μmol , translating to about 65–2105 g raw broccoli or 3/4 to 23 cups of raw broccoli.
eff↝, SFN-rich powders have been made by drying out broccoli sprout
IL1β↓,
IL6↓,
IL12↓,
TNF-α↓,
COX2↓,
CXCR4↓,
MPO↓,
HSP70/HSPA5↓,
HSP90↓,
VCAM-1↓,
IKKα↓,
NF-kB↓,
HO-1↑,
Casp3↑,
Casp7↑,
Casp8↑,
Casp9↑,
cl‑PARP↑,
Cyt‑c↑,
Diablo↑,
CHOP↑,
survivin↓,
XIAP↓,
p38↑,
Fas↑,
PUMA↑,
VEGF↓,
Hif1a↓,
Twist↓,
Zeb1↓,
Vim↓,
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Snail↓,
CD44↓,
cycD1↓,
cycA1↓,
CycB↓,
cycE↓,
CDK4↓,
CDK6↓,
p50↓,
P53↑,
P21↑,
GSH↑,
SOD↑,
GSTs↑,
mTOR↓,
Akt↓,
PI3K↓,
β-catenin/ZEB1↓,
IGF-1↓,
cMyc↓,

1725- SFN,    Anticancer Activity of Sulforaphane: The Epigenetic Mechanisms and the Nrf2 Signaling Pathway
- Review, Var, NA
*toxicity∅, Sulforaphane (SFN), a compound derived from cruciferous vegetables that has been shown to be safe and nontoxic, with minimal/no side effects
AntiCan↑, such as anticancer and antioxidant activities.
antiOx↑,
NRF2↑, FN also upregulates a series of cytoprotective genes by activating nuclear factor erythroid-2- (NF-E2-) related factor 2 (Nrf2), a critical transcription factor activated in response to oxidative stress;
DNMTs↓, SFN can reverse such epigenetic alterations in cancers by targeting DNA methyltransferases (DNMTs), histone deacetyltransferases (HDACs)
HDAC↓,
Hif1a↓, By suppressing the expression and activity of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), SFN inhibited the angiogenesis and metastasis of ovarian and colon cancers
VEGF↓,
P21↑, 15 μM SFN treatment caused reexpression of p21WAF1/CIP1 due to reduced expression of class I and II HDACs
TumCCA↑, resulted in cell cycle arrest
ac‑H3↑, upregulation of acetylated histone H3 and H4
ac‑H4↑,
DNAdam↑, SFN induced DNA damage
Dose↝, To achieve the effective inhibition of HDAC activity, it was reported that the concentration of SFN used in vitro experiments was from 3 to 15 μM, a single oral dose of 10 μmol in mice, and 68 g broccoli sprouts in human

1724- SFN,    Sulforaphane: A review of its therapeutic potentials, advances in its nanodelivery, recent patents, and clinical trials
- Review, Var, NA
antiOx↑, management of various diseases mainly due to its potent antioxidant properties.
NRF2↑, SFN achieves the activation of Nrf2 through the modification of cysteines of Kelch-like ECH-associated protein-1 (Keap1) resulting in the induction of phase-II (carcinogen-detoxifying) enzyme in cells
HDAC↓, SFN is known to inhibit the Histone deacetylases (HDACs) as well as Topoisomerases I and II enzymes, which play important roles during DNA replication.
neuroP↑, SFN upregulates the Nrf2 expression, thereby shows the neuroprotective efficacy.

1723- SFN,    Sulforaphane as a potential remedy against cancer: Comprehensive mechanistic review
- Review, Var, NA
*NRF2↑, activation of nuclear factor erythroid 2-related factor 2 (Nrf2). In this way, the oxidative stress and other toxicants are diminished
ROS↑, Cytotoxic effects of SFN are delivered via complex mechanisms where ROS generation results in improving apoptosis
MMP↓, ROS generation is also followed by mitochondrial membrane potential disruption that results in cytochrome c cytosolic release cleaving the poly-ADP-ribose polymerase and apoptosi
Cyt‑c↑,
cl‑PARP↑,
Apoptosis↑,
AMPK↑, AMPK signaling activated by SFN, high concentrations of ROS are produced
GSH↓, SFN-induced ROS generation also results in depletion of GSH levels

1722- SFN,    Sulforaphane as an anticancer molecule: mechanisms of action, synergistic effects, enhancement of drug safety, and delivery systems
- Review, Var, NA
TumCCA↑, arresting cell cycle in the G2/M and G1 phase
CYP1A1↓, Sulforaphane inhibits CYP1A1 and CYP3A4 and decease the activity of CYP3A4
CYP3A4↓,
Cyt‑c↑, release of cytochrome C from the mitochondria
Casp9↑,
Apoptosis↑,
ROS↑, generation of reactive oxygen species (ROS), and mitogen-activated protein kinases (MAPK)
MAPK↑,
P53↑, sulforaphane treatment increased p53 protein expression with associated increase in the protein levels of Bax
BAX↑,
ChemoSen↑, Combination therapies target multiple cell survival pathways, which results in synergism
HDAC↓, HDACi Histone deacetylase inhibition
GSH↓, fig 3
HO-1↑, They found that the protective effect of sulforaphane is mediated by the activation of the Keap1/Nrf2/ARE pathway, which consequently induce HO-1

3186- SFN,    A pharmacological inhibitor of NLRP3 inflammasome prevents non-alcoholic fatty liver disease in a mouse model induced by high fat diet
- in-vivo, Nor, NA
*NLRP3↓, suppression of NLRP3 inflammasome activation in the liver by SFN as evidenced by decrease in mRNA levels of ASC and caspase-1, caspase-1 enzyme activity, and IL-1β levels.
*ASC↓,
*Casp1↓,
*IL1β↓,
*ALAT↓, SFN treatment resulted in a reduction of the serum levels of ALT and AST increased by HFD
*AST↓,
*AMPK↑, Sulforaphane induces activation of the AMPK-autophagy axis in mouse primary hepatocytes
*mTOR↓, SFN reduced the phosphorylation of mTOR(Ser2448) in primary mouse hepatocytes (Fig. 4D), suggesting that SFN inhibited mTOR activation
*P70S6K↓, SFN suppression of mTOR activation was confirmed by a decrease in p70S6K1 phosphorylation, which is a downstream substrate of mTOR

3200- SFN,    Sulforaphane suppresses the activity of sterol regulatory element-binding proteins (SREBPs) by promoting SREBP precursor degradation
- in-vitro, Liver, HUH7
FASN↓, e sulforaphane (SFaN) impairs fatty acid synthase promoter activity and reduces SREBP target gene (e.g., fatty acid synthase and acetyl-CoA carboxylase 1) expression in human hepatoma Huh-7 cells
ACC↓,
SREBP1↓, SFaN reduced SREBP proteins by promoting the degradation of the SREBP precursor.

3199- SFN,    Sulforaphane improves chemotherapy efficacy by targeting cancer stem cell-like properties via the miR-124/IL-6R/STAT3 axis
- in-vitro, GC, NA
CSCs↓, It also plays important roles in mediating CSCs. For example, overexpression of miR-124 reduced neurosphere formation, CD133+ cell subpopulations, and stem cell markers such as BMI1, Nanog, and nestin in glioma cells
CD133↓,
BMI1↓,
Nanog↓,
Nestin↓,

3198- SFN,    Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells
- in-vitro, Pca, NA
Nanog↓, sulforaphane reduced the amount of Nanog, Sox2, E-cadherin, GATA-4, HNF-3β, SOX17, Otx2, TP63, Snail, VEGF R2 and HCG.
SOX2↓,
E-cadherin↓,
Snail↓,
VEGFR2↓,
Diff↓, sulforaphane, particularly in combination with TRAIL, reduces the levels of proteins required for self-renewal, differentiation, cell migration, the epithelialmesenchymal transition (EMT) and tumorigenesis (
TumCMig↓,
EMT↓,
CXCR4↓, CXCR4 receptor, which is involved in migration and metastasis (42), was inhibited following the sulforaphane-only treatment
NOTCH1↓, Similar results were found for the Notch 1 receptor
ALDH1A1↓, Sulforaphane significantly reduced the ALDH1 activity from ∼30 to 12%; conversely
CSCs↓, data suggest that sulforaphane strongly inhibits stem cell signaling
eff↑, demonstrated that sulforaphane and TRAIL reduced the expression of the CSC markers CD133, CXCR4, Nanog, c-Met, EpCAM, CD44, and ALDH1 and the proliferation marker Ki67;

3197- SFN,    Sulforaphane Inhibits Self-renewal of Lung Cancer Stem Cells Through the Modulation of Polyhomeotic Homolog 3 and Sonic Hedgehog Signaling Pathways
- in-vitro, Lung, A549 - in-vitro, Lung, H460
TumCP↓, SFN inhibited the proliferation of lung cancer cells and lung cancer stem cells simultaneously.
CSCs↓,
Shh↓, SFN inhibited the activity of PHC3 and SHH signaling pathways in the lung cancer stem cells
Smo↓, SFN can obviously reduce the mRNA and protein expression of ShhSmo and Gli1 in CD133-positive cells as compared to CD133-negative cells
Gli1↓,

3196- SFN,    Sulforaphane eradicates pancreatic cancer stem cells by NF-κB
- Review, PC, NA
CSCs↓, Sulforaphane eradicates pancreatic cancer stem cells by NF-κB
NF-kB↓,

3195- SFN,    AKT1/HK2 Axis-mediated Glucose Metabolism: A Novel Therapeutic Target of Sulforaphane in Bladder Cancer
- in-vitro, Bladder, UMUC3
ATP↓, SFN strongly downregulates ATP production by inhibiting glycolysis and mitochondrial oxidative phosphorylation (OXPHOS).
Glycolysis↓,
OXPHOS↓,
HK2↓, SFN weaken the glycolytic flux by suppressing multiple metabolic enzymes, including hexokinase 2 (HK2) and pyruvate dehydrogenase (PDH).
PDH↓,
AKT1↓, SFN decreases the level of AKT1 and p-AKT ser473 , especially in low-invasive UMUC3 cells.
p‑Akt↓,

3194- SFN,    Sulforaphane impedes mitochondrial reprogramming and histone acetylation in polarizing M1 (LPS) macrophages
- in-vitro, Nor, NA
*OXPHOS↑, suggesting that OXPHOS activity is needed for maximal inhibition of M1 marker expression by Sfn
*M1↓,
*IL1β↓, Consistent with our previous study [40], presence of Sfn significantly diminished mRNA expression of il1β, il6, nos2, and tnfα in M1 (LPS) cells
*IL6↓,
*NOS2↓,
*TNF-α↓,
*ROS↓, 0 and 10 μM, impaired M1 marker expression, ROS or NO production and preserved respiratory activity after LPS exposure
*NO↓,
*ACC↑, Sfn prevents the drop of nuclear and cytosolic acetyl-CoA in LPS-stimulated macrophages

3193- SFN,    Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress
- Review, Var, NA
DNMTs↓, SFN, a natural phytochemical, primarily attenuates both DNMTs and HDACs, individually suppressing DNA hypermethylation and histones deacetylation, ultimately upregulating NRF2.
HDAC↑,
NRF2↑,
DNMT1↓, significant attenuation of DNMT1 and DNMT3a contributed to a decrease in the methylated CpG ratio in the NFE2L2 promoter region in an SFN dose- and time-dependent manner, thus increasing NRF2
DNMT3A↓,
NQO1↑, consequently increasing the transcription of its target genes such as NQO1 and catechol-O-methyltransferase (COMT)
COMT↑,
TumCG↓, SFN may prevent or slow the growth of recurrent prostate cancer, essentially without severe adverse events.
*toxicity↓,

3192- SFN,    Transcriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention
- in-vitro, Pca, PC3
Sp1/3/4↓, Sp1 protein was significantly decreased by SFN treatment in prostate cancer cells . Because SFN decreased the expression of Sp1, and to a lesser extent Sp3
selectivity↑, SFN alters gene expression differentially in normal and cancer cells with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent.
NRF2↑, through the induction of phase 2 enzymes via Keap1-Nrf2 signaling
HDAC↓, SFN also inhibits the activity and/or expression of genes that regulate epigenetic mechanisms including histone deactylases (HDACs) and DNA methyltransferases (DNMTs) in cancer cells
DNMTs↓,
TumCCA↑, 15 μM SFN treatment induces cell cycle arrest at the G1 phase and only modestly increases apoptosis
selectivity↑, Normal prostate epithelial cells (PREC) do not undergo cell cycle arrest or apoptosis in response to this SFN treatment
HO-1↑, In all cell lines and time points, HO1 and NQO1 were identified as significantly upregulated by SFN
NQO1↑,
CDK2↓, MX non-receptor tyrosine kinase (BMX), cyclin-dependent kinase 2 (CDK2), and polo-like kinase 1 (PLK1) had decreased expression with SFN treatment
TumCP↓, suppression of Sp1 expression decreased prostate cancer cells proliferation.
BID↑, SFN treatment produced a significant increase in the expression of the apoptosis related genes Bid, Smac/Diablo, and ICAD only in PC-3 cells (
Smad1↑,
Diablo↑,
ICAD↑,
Cyt‑c↑, It also increased the expression of cytochrome c, c-IAP1, and HSP27 in PC-3 cells while it decreased expression in PREC cells.
IAP1↑,
HSP27↑,
*Cyt‑c↓,
*IAP1↓,
*HSP27↓,
survivin↓, In these studies, inhibition of Sp1 is associated with inhibition of the cancer promoting genes survivin, CDK4, VEGF and the androgen receptor.
CDK4↓,
VEGF↓,
AR↓,

3191- SFN,    Sulforaphane exhibits potent renoprotective effects in preclinical models of kidney diseases: A systematic review and meta-analysis
- Review, NA, NA
Prot↝, SFN administration (median dose: 2.5 mg/kg, median duration: 3 weeks) significantly decreased urinary protein excretion (SMD -2.20 [-2.68; -1.73], P < 0.0001, I2 = 34.1 %).
RenoP↑, It further improved two kidney lesion histological indices namely kidney fibrosis (SMD -3.08 [-4.53; -1.63], P < 0.0001, I2 = 73.7 %) and glomerulosclerosis

3190- SFN,    Sulforaphane inhibits TGF-β-induced fibrogenesis and inflammation in human Tenon’s fibroblasts
- in-vitro, Nor, NA
*Fibronectin↓, by inhibiting the production of fibronectin and the expression of α-SMA.
*α-SMA↓,
*ITGB1↓, SFN treatment reduced the expression of TGF-β-promoted integrins β1 and α5, myosin light chain (MLC) phosphorylation, and stress fiber formation, as well as the expression of IL-6, IL-8, and CTGF.
*ITGA5↓,
*IL6↓,
*IL8↓,
Inflam↓, SFN has potent anti-fibrotic and anti-inflammatory effects in HTFs and is a potential candidate for subconjunctival fibrosis therapy.

3189- SFN,    Sulforaphane Inhibits TNF-α-Induced Adhesion Molecule Expression Through the Rho A/ROCK/NF-κB Signaling Pathway
- in-vitro, Nor, ECV304
*ICAM-1↓, SFN attenuated TNF-α-induced expression of ICAM-1 in ECV 304 cells
*IL1β↓, Pretreatment of ECV 304 cells with SFN inhibited dose-dependently the secretion of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and IL-8
*IL6↓,
*IL8↓,
*p‑IKKα↓, SFN decreased TNF-α-mediated phosphorylation of IκB kinase (IKK) and IκBα, Rho A, ROCK, ERK1/2, and plasminogen activator inhibitor-1 (PAI-1) levels.
*Rho↓,
*ROCK1↓,
*ERK↓,
*Inflam↓, beneficial effects of SFN on suppression of inflammation within the atherosclerotic lesion.

3188- SFN,    Sulforaphane inhibited tumor necrosis factor-α induced migration and invasion in estrogen receptor negative human breast cancer cells
- in-vitro, BC, NA
TNF-α↓, Sulforaphane significantly (p<0.05) inhibited tumor necrosis factor (TNF)-α induced cellular migration and invasion in MCF10DCIS.com human breast cancer cells, compared with controls.
TumCI↓,
TumMeta↓,
MMPs↓, MMPs, including MMP-2, MMP-9, and MMP-13, and the enzymatic activities of MMP-2 and MMP-9 were suppressed by sulforaphane treatments at 1, 5, and 10 μM concentration
MMP2↓,
MMP9↓,
MMP13↓,

3187- SFN,    Sulforaphane inhibits the expression of interleukin-6 and interleukin-8 induced in bronchial epithelial IB3-1 cells by exposure to the SARS-CoV-2 Spike protein
- in-vitro, Nor, IB3-1
*IL6↓, SFN inhibits, in cultured IB3-1 bronchial cells, the gene expression of IL-6 and IL-8 induced by the S-protein of SARS-CoV-2.
*IL8↓,
*Inflam↓, SFN can be employed in protocols useful to control hyperinflammatory state associated with SARS-CoV-2 infection.

2447- SFN,    Sulforaphane Bioavailability from Glucoraphanin-Rich Broccoli: Control by Active Endogenous Myrosinase
- Review, Nor, NA
*BioAv↓, when either broccoli sprouts or seeds are administered directly to subjects without prior extraction and consequent inactivation of endogenous myrosinase, the sulforaphane in those preparations is 3-4-fold more bioavailable than sulforaphane from gl
*BioAv↓, sulforaphane is only moderately stable over time, especially in aqueous solution
*BioAv↓, their useful shelf-life is limited unless chemically stabilized, kept cold, or made frequently during the study
*BioAv↝, see Table 1 for interesing bioavailable information of different forms

3185- SFN,    Sulforaphane decreases oxidative stress and inhibits NLRP3 inflammasome activation in a mouse model of ulcerative colitis
- in-vivo, Nor, RAW264.7
*IL18↓, SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1β, substantially inhibiting NLRP3 activation, and decreasing inflammation.
*IL1β↓,
*NLRP3↓,
*Inflam↓,

3184- SFN,    The Integrative Role of Sulforaphane in Preventing Inflammation, Oxidative Stress and Fatigue: A Review of a Potential Protective Phytochemical
- Review, Nor, NA
*NRF2↑, SFN treatment modulates redox balance via activating redox regulator nuclear factor E2 factor-related factor (Nrf2).
*Inflam↓, SFN reduces inflammation by suppressing centrally involved inflammatory regulator nuclear factor-kappa B (NF-κB),
*NF-kB↓,
*ROS↓, SFN in preventing fatigue, inflammation, and oxidative stress,
*BioAv↝, It was identified that the lowest oral dose of SFN (2.8 µmol/kg or 0.5 mg/kg) has an absolute bioavailability of more than 80%, whilst with the highest dose (28 µmol/kg or 5 mg/kg) had only 20% bioavailability
*BioAv↝, For example, quickly steaming broccoli sprouts, followed by myrosinase treatment, contains the highest amount SFN, which is approximately 11 and 5 times higher than freeze dried and untreated steamed broccoli sprouts, respectively
*BioAv↝, The peak concentration of SFN metabolites (1.91 ± 0.24 µM) was identified in urine after 1 h of oral dose (200 µmol) of broccoli sprout ITCs to four healthy human volunteers
*BioAv↝, study with 20 participants, providing 200 µmol of SFN in capsule form revealed a peak of SFN equivalence (0.7 ± 0.2 µM) at 3 h
*cardioP↑, FN actives signaling pathways and phosphorylates Nrf2, which further increases the expression and activity of phase 2 enzymes, such as GR, GST, TR, NQO1, to minimize cardiac cell arrest,
*GPx↑, 200 mg of dried broccoli sprouts increased glutathione content, decreased levels of oxidized glutathione, increased the activity of GR and glutathione peroxidase (GPx), which are associated with decreasing oxidative stress in the cardiovascular syst
*SOD↑, SFN treatment activates Nrf2, which translocates into the nucleus to induce production of cellular defense enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), heme oxygenase (HO) 1, NADPH quinone oxidoreductase
*Catalase↑,
*GPx↑,
*HO-1↑,
*NADPH↑,
*NQO1↑,
*LDH↓, Furthermore, creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) (two enzymatic markers to assess muscle damage) were significantly lower after SFN treatment compared to a placebo
*hepatoP↑, protects exercise-induced liver damage, evidenced by reducing blood levels of enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), via inducing antioxidant defense response
*ALAT↓,
*AST↓,
*IL6↓, fresh broccoli sprouts (30 g/day) daily for 10 weeks. After the intervention period, plasma IL-6 concentrations were significantly lower

3183- SFN,    Sulforaphane potentiates the efficacy of chemoradiotherapy in glioblastoma by selectively targeting thioredoxin reductase 1
- in-vitro, GBM, NA
RadioS↑, SFN synergistically improves chemoradiotherapy efficacy in GBM cells
TrxR1↓, Herein, we demonstrate that sulforaphane (SFN), an isothiocyanate phytochemical with anti-cancer effects, inhibits the activity of thioredoxin reductase 1 (TrxR1)
ROS↑, This inhibition of TrxR1 leads to the accumulation of reactive oxygen species (ROS), thereby enhancing chemoradiotherapy-induced apoptosis in GBM cells.
ChemoSen↑,
Prx↓, Impaired/reduced function(ai)

3182- SFN,    Sulforaphane Modulates AQP8-Linked Redox Signalling in Leukemia Cells
- in-vitro, AML, NA
Prx↓, The results show that the cell treatment with 10 μM SFN for 24 h significantly decreased Prx-1 expression.
AQPs↓, Results indicated that sulforaphane inhibited both aquaporin-8 and Nox2 expression, thus decreasing B1647 cells viability.
NOX↓,
tumCV↓,
AntiCan↑, In addition to its well-known anticancer activity [2], SFN has been demonstrated to possess cardioprotective [3], neuroprotective [4], and anti-inflammatory activities
cardioP↑,
neuroP↑,
Inflam↓,
chemoP↑, potent chemopreventive effect of SFN is based on its ability to target multiple mechanisms within the cell to control carcinogenesis
angioG↓, SFN prevents uncontrolled cancer cell proliferation through the modulation of genes involved in apoptosis and cell cycle arrest [5, 8], angiogenesis [9, 10], and metastasis
TumMeta↓,
selectivity↑, SFN is able to selectively exert cytotoxic effects in many human cancer cells without affecting normal cells
ROS↓, Results in Figure 4 show that only 10 μM SFN treatment causes a significant decrease of ROS intracellular levels in respect to control cells,

3181- SFN,    Effect of sulforaphane on protein expression of Bip/GRP78 and caspase-12 in human hapetocelluar carcinoma HepG-2 cells
- in-vitro, HCC, HepG2
GRP78/BiP↑, SFN can up-regulate the expression of Bip/GRP78 and caspase-12,by which induce apoptosis of HepG-2 cells through the endoplasmic reticulum pathway.
Casp12↑,
Apoptosis↑,
ER Stress↑,

3180- SFN,    Exploring the therapeutic effects of sulforaphane: an in-depth review on endoplasmic reticulum stress modulation across different disease contexts
- Review, Var, NA
*cardioP↑, broad range of protective functions of sulforaphane, improving various diseases, such as cardiovascular, central nervous system, liver, eye, and reproductive diseases, as well as diabetes, cancer, gastroenteritis, and osteoarthritis,
*ER Stress↓, through the amelioration of ER stress in both in vivo and in vitro studies.
GRP78/BiP↑, Sulforaphane significantly increased the level of Bip/GRP78, and XBP-1 protein expression and enhanced the rate of HepG2 cells apoptosis.
XBP-1↑,
Apoptosis↑,
*NRF2↑, Mitigates oxidative stress and ER stress in vascular cells, contributing to cardioprotection
UPR↑, SFN can drive the UPR into an overactivated state(ai)

2556- SFN,    The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review
- Review, Var, NA
chemoP↑, sulforaphane (SFN) has surfaced as a particularly potent chemopreventive agent based on its ability to target multiple mechanisms within the cell to control carcinogenesis
HDAC↓, SFN's chemopreventative properties was also demonstrated in another study, where through its HDACi activity,
Hif1a↓, SFN inhibits hypoxia inducible factor-1 α (HIF-1α) and c-Myc, two angiogenesis- associated transcription factors
angioG↓,
CYP1A1↓, CYP1A1 reduction, MFC7
eff↑, Kallifatidis et al. reported SFN to potentiate the anti-cancer effects of cisplatin, gemcitabine, doxorubicin or 5-flurouracil on prostate cancer cell line MIA-PaCa2 while also increasing cytotoxicity of cancer stem cells
BioAv↑, Shapiro et al. reported that the chewing of fresh broccoli sprouts increases the interaction of glucosinolates with myrosinase and consequently, increases the bioavailability of SFN in the body (Shapiro et al. 2001).

2555- SFN,    Chemopreventive functions of sulforaphane: A potent inducer of antioxidant enzymes and apoptosis
- Review, Var, NA
chemoP↑, induction of Metallothioneins MT by sulforaphane as a strategy for achieving chemoprevention and chemoprotection.
HDAC↓, sulforaphane supplementation resulted in slower tumor growth and significant histone deacetylase (HDAC) inhibition in the xenografts,
TumCCA↑, HDAC inhibition represents a novel chemoprevention mechanism by which sulforaphane can promote cell cycle arrest and apoptosis.
Apoptosis↑,
Mets↑, induction of Metallothioneins MT by sulforaphane
*NRF2↑, We have shown that sulforaphane can activate Nrf2 ...suggesting that increased expression of Nrf2 protein may play a key role in sulforaphane-induced MT gene activation.
ROS⇅, exposure to high concentrations of sulforaphane might generate an oxidant signal to stimulate caspase 3 pathway activation and DNA fragmentation, leading to cell death.

2554- SFN,    Sulforaphane (SFN): An Isothiocyanate in a Cancer Chemoprevention Paradigm
- Review, Var, NA
Dose↝, In human subjects given single doses of 200 μmol broccoli sprouts ITC preparation, ITC plasma concentrations peaked between 0.943 and 2.27 μmol/L 1 h after feeding, with half-life of 1.77 ± 0.13 h suggesting the possibility of clinical intervention a
chemoP↑, present review provides the current understanding of the cancer chemopreventive pharmacology of sulforaphane towards its potential as an anticancer agent.
*NQO1↑, sulforaphane upregulated the expression of NQO1, GST and GCL in the small intestine of wildtype mice
*GSTA1↑,
HDAC↓, Sulforaphane as Inhibitor of HDACs Challenges the Pro-Oncogenic Epigenetic Pattern in Cancer Cells
NF-kB↓, In a study on prostate cancer cells, treatment with SFN (20 and 30 μM) significantly inhibited NF-κB

2553- SFN,    Mechanistic review of sulforaphane as a chemoprotective agent in bladder cancer
- Review, Bladder, NA
antiOx↓, SFN is a bioactive compound with both antioxidant and anti-inflammatory properties.
Inflam↓,
ChemoSen↑, SFN also improves the efficacy of certain traditional chemotherapeutic regimens
ROS⇅, A lesser established mechanism proposed by Li, et al. is that SFN induces mild increases ROS, leading to transcription factor EB (TFEB) activation. TFEB plays a role in activating antioxidant response elements and...ultimately reducing overall oxidat
*NRF2↑, SFN treatment increased Nrf2 and, therefore, glutathione levels
*GSH↑,
Catalase↑, Cancer cells treated with SFN showed higher catalase levels, heme oxygenase 1, and NAD(P)
HO-1↑,
NAD↑,
chemoP↑, Taken together, these studies provide strong evidence for the chemoprotective nature of SFN in various human epithelial cancers, including those of the bladder.

1507- SFN,    Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects
- in-vivo, Colon, NA - Human, Nor, NA
TumCG↓, When consumed in the diet at an average daily dose of 7.5 mumol per animal for 21 days, SFN suppressed the growth of human PC-3 prostate cancer cells by 40% in male nude mice.
HDAC↓, significant decrease in HDAC activity
*BioAv↑, a single dose of 68 g BroccoSprouts inhibited HDAC activity significantly in peripheral blood mononuclear cells (PBMC) 3 and 6 hrs following consumption.
Dose∅, a single dose of 68 g BroccoSprouts inhibited HDAC activity significantly in peripheral blood mononuclear cells (PBMC) 3 and 6 hrs following consumption.
Half-Life∅, a single dose of 68 g BroccoSprouts inhibited HDAC activity significantly in peripheral blood mononuclear cells (PBMC) 3 and 6 hrs following consumption.

2449- SFN,    Optimization of a blanching step to maximize sulforaphane synthesis in broccoli florets
- Study, Nor, NA
BioAv↑, Optimal blanching condition was immersion in water at 57° for 13 min.coinciding with the minimum glucosinolates and glucoraphanin content, and with the maximum myrosinase. Sulforaphane content was increased by 237% compared with fresh broccoli.

2448- SFN,    Sulforaphane and bladder cancer: a potential novel antitumor compound
- Review, Bladder, NA
Apoptosis↑, Recent studies have demonstrated that Sulforaphane not only induces apoptosis and cell cycle arrest in BC cells, but also inhibits the growth, invasion, and metastasis of BC cells
TumCG↓,
TumCI↓,
TumMeta↓,
glucoNG↓, Additionally, it can inhibit BC gluconeogenesis
ChemoSen↑, demonstrate definite effects when combined with chemotherapeutic drugs/carcinogens.
TumCCA↑, SFN can block the cell cycle in G2/M phase, upregulate the expression of Caspase3/7 and PARP cleavage, and downregulate the expression of Survivin, EGFR and HER2/neu
Casp3↑,
Casp7↑,
cl‑PARP↑,
survivin↓,
EGFR↓,
HER2/EBBR2↓,
ATP↓, SFN inhibits the production of ATP by inhibiting glycolysis and mitochondrial oxidative phosphorylation in BC cells in a dose-dependent manner
Glycolysis↓,
mt-OXPHOS↓,
AKT1↓, dysregulation of glucose metabolism by inhibiting the AKT1-HK2 axis
HK2↓,
Hif1a↓, Sulforaphane inhibits glycolysis by down-regulating hypoxia-induced HIF-1α
ROS↑, SFN can upregulate ROS production and Nrf2 activity
NRF2↑,
EMT↓, inhibiting EMT process through Cox-2/MMP-2, 9/ ZEB1 and Snail and miR-200c/ZEB1 pathways
COX2↓,
MMP2↓,
MMP9↓,
Zeb1↓,
Snail↓,
HDAC↓, FN modulates the histone status in BC cells by regulating specific HDAC and HATs,
HATs↓,
MMP↓, SFN upregulates ROS production, induces mitochondrial oxidative damage, mitochondrial membrane potential depolarization, cytochrome c release
Cyt‑c↓,
Shh↓, SFN significantly lowers the expression of key components of the SHH pathway (Shh, Smo, and Gli1) and inhibits tumor sphere formation, thereby suppressing the stemness of cancer cells
Smo↓,
Gli1↓,
BioAv↝, SFN is unstable in aqueous solutions and at high temperatures, sensitive to oxygen, heat and alkaline conditions, with a decrease in quantity of 20% after cooking, 36% after frying, and 88% after boiling
BioAv↝, It has been reported that the ability of individuals to use gut myrosinase to convert glucoraphanin into SFN varies widely
Dose↝, Excitingly, it has been reported that daily oral administration of 200 μM SFN in melanoma patients can achieve plasma levels of 655 ng/mL with good tolerance

1452- SFN,    Sulforaphane Suppresses the Nicotine-Induced Expression of the Matrix Metalloproteinase-9 via Inhibiting ROS-Mediated AP-1 and NF-κB Signaling in Human Gastric Cancer Cells
- in-vitro, GC, AGS
MMP9↓, Sulforaphane effectively suppressed ROS, p38 MAPK, Erk1/2, AP-1, and NF-κB activation by inhibiting MMP-9 expression in gastric cancer AGS cells.
p38↓,
ERK↓,
AP-1↓,
ROS↓, results indicate that sulforaphane suppressed the nicotine-induced MMP-9 via regulating ROS generation in human gastric cancer AGS cells ( by Inhibiting ROS Generation)
NF-kB↓, Sulforaphane Suppresses Nicotine-Induced MMP-9 Expression by Inhibiting Reporter Activities of AP-1 and NF-κB
TumCI↓,
MMP9↓, Suppressing MMP-9 Expression
HDAC↓, Rutz et al. reported that sulforaphane acts as a histone deacetylase (HDAC) inhibitor to prostate cancer cell progression
Glycolysis↓, sulforaphane decreased glycolytic metabolism in a hypoxia microenvironment by inhibiting hypoxia-induced HIF-1α
Hif1a↓,
*memory↑, Sulforaphane could prevent memory dysfunction and improve cognitive function
*cognitive↑,

1466- SFN,    Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway
- vitro+vivo, Thyroid, FTC-133
TumCP↓,
TumCCA↑, G2/M phase
Apoptosis↑,
TumCMig↓,
TumCI↓,
EMT↓,
Slug↓,
Twist↓,
MMP2↓,
MMP9↓,
TumCG↓,
p‑Akt↓,
P21↑,
ERK↑,
p38↑,
ROS↑, ROS was significantly induced in both FTC133 and K1 cells when cells were treated with 40 μM SFN for 4 h Several previous studies have shown that SFN induces ROS
*toxicity∅, we did not find significant effect of SFN on body weight and liver function of mice.
MMP↓,
eff↓, Like NAC, ASC treatment significantly attenuated anti-proliferative effect of SFN in these two cell lines

1465- SFN,    TRAIL attenuates sulforaphane-mediated Nrf2 and sustains ROS generation, leading to apoptosis of TRAIL-resistant human bladder cancer cells
- NA, Bladder, NA
eff↑, Combined treatment with SFN and TRAIL (SFN/TRAIL) significantly induced apoptosis
Apoptosis↑,
Casp↑,
MMP↓,
BID↑,
DR5↑,
ROS↑, SFN increased both the generation of reactive oxygen species (ROS) and the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which is an anti-oxidant enzyme.
NRF2↑,
eff↑, Interestingly, TRAIL effectively suppressed SFN-mediated nuclear translocation of Nrf2, and the period of ROS generation was more extended compared to that of treatment with SFN alone.
eff↓, blockade of ROS generation inhibited apoptotic activity

1464- SFN,    d,l-Sulforaphane Induces ROS-Dependent Apoptosis in Human Gliomablastoma Cells by Inactivating STAT3 Signaling Pathway
- in-vitro, GBM, NA
Apoptosis↑,
Casp3↑,
BAX↑,
Bcl-2↓,
ROS↑, SFN treatment led to increase the intracellular reactive oxygen species (ROS) level in GBM cells
p‑STAT3↓,
JAK2↓,
eff↓, blockage of ROS production by using the ROS inhibitor N-acetyl-l-cysteine totally reversed SFN-mediated down-regulation of JAK2/Src-STAT3 signaling activation and the subsequent effects on apoptosis

1463- SFN,    Sulforaphane induces reactive oxygen species-mediated mitotic arrest and subsequent apoptosis in human bladder cancer 5637 cells
- in-vitro, Bladder, 5637
tumCV↓,
CycB↑, concomitant increased complex between cyclin B1 and Cdk1
p‑CDK1↑, of cyclin B1 and phosphorylation of Cdk1
Apoptosis↑,
Casp8↑,
Casp9↑,
Casp3↑,
cl‑PARP↑,
ROS↑, maximum level of ROS accumulation was observed 3h after sulforaphane treatment.
eff↓, ROS scavenger, N-acetyl-L-cysteine, notably attenuated sulforaphane-mediated apoptosis as well as mitotic arrest

1462- SFN,    Epithelial-mesenchymal transition, a novel target of sulforaphane via COX-2/MMP2, 9/Snail, ZEB1 and miR-200c/ZEB1 pathways in human bladder cancer cells
- in-vitro, Bladder, T24
EMT↓,
TumCI↓,
TumCMig↓,
E-cadherin↑,
Zeb1↓,
Snail↓,
COX2↝,
MMP2↝,
MMP9↝,

1461- SFN,    Targets and mechanisms of sulforaphane derivatives obtained from cruciferous plants with special focus on breast cancer - contradictory effects and future perspectives
- Review, BC, NA
TumCP↓,
Apoptosis↑,
TumCCA↑,
antiOx↑,
NA↑,

1460- SFN,    High levels of EGFR prevent sulforaphane-induced reactive oxygen species-mediated apoptosis in non-small-cell lung cancer cells
- in-vitro, Lung, NA
ROS↑, Sulforaphane (SFN) has been shown to induce the production of reactive oxygen species (ROS) and inhibit epidermal growth factor receptor (EGFR)
EGFR↓,
eff↓, We present evidence that cells with high-level EGFR expression (CL1-5) are more resistant to SFN treatment than those with low-level expression (CL1-0)
TumCCA↑, S-phase
γH2AX↑,
DNAdam↑,
eff↓, Pretreatment with the antioxidant N-acetyl-L-cysteine prevented SFN-induced apoptosis in CL1-0 cells and production of γH2AX in both CL1-0 and CL1-5 cells.

1459- SFN,  Aur,    Auranofin Enhances Sulforaphane-Mediated Apoptosis in Hepatocellular Carcinoma Hep3B Cells through Inactivation of the PI3K/Akt Signaling Pathway
- in-vitro, Liver, Hep3B - in-vitro, Liver, HepG2
eff↑, sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity and cell proliferation compared to either single treatment
TumCCA↑, Sub-G1 cells
Apoptosis↑,
MMP↓,
BAX↑,
cl‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
ROS↑, combined treatment induced excessive generation of reactive oxygen species (ROS)
eff↓, treatment with N-acetyl-L-cysteine, a ROS scavenger, reduced combined treatment-induced ROS production and apoptosis.
PI3K↓,
Akt↓,
TrxR↓, treatment with either sulforaphane or auranofin alone at low concentrations weakly inhibit TrxR activity Combined treatment significantly reduced TrxR activity and cell viability
BAX↑,
Bcl-2∅,

1458- SFN,    Sulforaphane Impact on Reactive Oxygen Species (ROS) in Bladder Carcinoma
- Review, Bladder, NA
HDAC↓, SFN’s role as a natural HDAC-inhibitor is highly relevant
eff↓, SFN exerts stronger anti-proliferative effects on bladder cancer cell lines under hypoxia, compared to normoxic conditions
TumW↓, mice, SFN (52 mg/kg body weight) for 2 weeks reduced tumor weight by 42%
TumW↓, In another study a 63% inhibition was noted when tumor bearing mice were treated with SFN (12 mg/kg body weight) for 5 weeks
angioG↓,
*toxicity↓, In both investigations, the administration of SFN did not evoke apparent toxicity
GutMicro↝, SFN may protect against chemical-induced bladder cancer by normalizing the composition of gut microbiota and repairing pathophysiological destruction of the gut barrier,
AntiCan↑, A prospective study involving nearly 50,000 men indicated that high cruciferous vegetable consumption may reduce bladder cancer risk
ROS↑, Evidence shows that SFN upregulates the ROS level in T24 bladder cancer cells to induce apoptosis
MMP↓,
Cyt‑c↑,
Bax:Bcl2↑,
Casp3↑,
Casp9↑,
Casp8∅,
cl‑PARP↑,
TRAIL↑, ROS generation promotes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity
DR5↑,
eff↓, Blockade of ROS generation inhibited apoptotic activity and prevented Nrf2 activation in cells treated with SFN, pointing to a direct effect of ROS on apoptosis
NRF2↑, SFN potently inhibits carcinogenesis via activation of the Nrf2 pathway
ER Stress↑, endoplasmic reticulum stress evoked by SFN
COX2↓, downregulates COX-2 in T24 cells
EGFR↓, downregulation of both the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2/neu
HER2/EBBR2↓,
ChemoSen↑, gemcitabine/cisplatin and SFN triggered pathway alterations in bladder cancer may open new therapeutic strategies, including a combined treatment regimen to cause additive effects.
NF-kB↓,
TumCCA?, cell cycle at the G2/M phase
p‑Akt↓,
p‑mTOR↓,
p70S6↓,
p19↑, p19 and p21, are elevated under SFN
P21↑,
CD44↓, CD44s expression correlates with induced intracellular levels of ROS in bladder cancer cells variants v3–v7 on bladder cancer cells following SFN exposure

1457- SFN,    Sulforaphane Inhibits IL-1β-Induced IL-6 by Suppressing ROS Production, AP-1, and STAT3 in Colorectal Cancer HT-29 Cells
- in-vitro, CRC, HT-29
IL6↓, Sulforaphane inhibits the expression of IL-6 in HT-29 cells by inhibiting the production of ROS
ROS↓, reduces oxidative stress by curtailing reactive oxygen species (ROS) production.
TumCP↓,
TumCI↓,
p38↓,
AP-1↓,

1456- SFN,    Sulforaphane regulates cell proliferation and induces apoptotic cell death mediated by ROS-cell cycle arrest in pancreatic cancer cells
- in-vitro, PC, MIA PaCa-2 - in-vitro, PC, PANC1
tumCV↓,
TumCP↓,
cl‑PARP↑,
cl‑Casp3↑,
TumCCA↑, accumulation in the sub G1 phase
ROS↑, SFN caused a considerable increase in ROS in MIA PaCa-2 and PANC-1 cells as compared to the control group
MMP↓, SFN increased ROS level and γH2A.X expression while decreasing mitochondrial membrane potential (ΔΨm).
γH2AX↑,
eff↓, (NAC) was shown to reverse SFN-induced cytotoxicity and ROS level.
*toxicity↓, HUVECs, used as normal control cells, did not show significant inhibitory effects at SFN concentrations below 20 μM

1455- SFN,    Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress
- in-vitro, Cerv, HeLa - in-vitro, Nor, 1321N1
*ROS↓, SFN may trigger a self-defense cellular mechanism that can effectively mitigate oxidative stress commonly associated with many metabolic and age-related diseases. SFN treatment prevented CCCP-induced ROS increases in WT 1321N1 cells(normal)
*BioAv↑, Tissue concentrations of SFN can reach 3–30 μM upon broccoli consumption
LC3II↑, SFN (15 μM, 3–9 h) treatment markedly increased endogenous LC3-II levels in HeLa cells
LAMP1?, gradual (within hours) increases in the expression of LAMP1 proteins upon SFN (15 μM, 3–9 h) treatment in HeLa cells
TumAuto↑, SFN led to enhanced lysosomal and autophagic function.
TFEB↑, SFN (10–15 μM) treatment for 4 h induced nuclear translocation of endogenous TFEB in HeLa cells
ROS↑, SFN treatment for 2 h resulted in a mild increase of intracellular ROS. ROS mediate some effects of SFN
eff↓, NAC (5 mM), a commonly used membrane-permeable antioxidant compound [7], prevented SFN-induced increases in ROS

1454- SFN,    Absorption and chemopreventive targets of sulforaphane in humans following consumption of broccoli sprouts or a myrosinase-treated broccoli sprout extract
- Human, Nor, NA
*HDAC↓, SFN metabolites were reported to inhibit histone deacetylases (HDAC)
*eff↑, Plasma and urinary levels of total SFN metabolites were ~3–5 times higher in sprout consumers compared to BSE consumers
*eff↑, In sprout consumers (Fig. 2C inset), plasma concentrations were 2.4-fold higher after consuming the second dose than after the first dose.
*eff↑, Compared to the BSE, raw sprouts likely contain more fiber, which can slow gut transit and increase contact time between SFN and absorptive surfaces in the proximal gut.
*BioAv↑, Sprout 127.6 grams = 205uM±19.9 content yields SFN 0.5 to 2uM in plasma
*BioAv↑, Differences in SFN bioavailability among ingested forms of broccoli have largely been attributed to differences in myrosinase activity. Subjects consuming raw broccoli or broccoli sprouts containing intact myrosinase have higher recovery

1453- SFN,    Sulforaphane Reduces Prostate Cancer Cell Growth and Proliferation In Vitro by Modulating the Cdk-Cyclin Axis and Expression of the CD44 Variants 4, 5, and 7
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
TumCG↓,
TumCP↓,
TumCCA↑, cell cycle arrest at the S- and G2/M-phase
H3↑,
H4↑,
HDAC↓, SFN acts as a histone deacetylase (HDAC) inhibitor.
CDK1↑, With 10 µM SFN, CDK1 and CDK2 increased in both cell lines,
CDK2↑,
p19↑,
*BioAv↑, A transient decrease in HDAC activity has also been observed in healthy humans 3 h after providing a daily 200 µM SFN dose, resulting in a plasma concentration of SFN metabolites of 0.1–0.2 µM

1467- SFN,    Sulforaphane generates reactive oxygen species leading to mitochondrial perturbation for apoptosis in human leukemia U937 cells
- in-vitro, AML, U937
Apoptosis↑,
ROS↑,
MMP↓, collapse of MMP
Casp3↑,
Bcl-2↓,
eff↓, quenching of ROS generation with antioxidant N-acetyl-L-cysteine conferred significant protection against sulforaphane-elicited ROS generation, disruption of the MMP, caspase-3 activation and apoptosis.

1437- SFN,    Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition
- Review, NA, NA
HDAC↓, 15 μM
HDAC1↓,
HDAC2↓,
HDAC3↓,
HDAC8↓,
eff↑, this evidence suggests that sulforaphane may also compromise DNA repair mechanisms in cancer cells with selectivity.
ac‑HSP90↑,
DNMT1↓, 10 μM sulforaphane in 6 days inhibited DNMT1 and DNMT3a expression by 48% and 78%, respectively
DNMT3A↓,
hTERT↓,
NRF2↑, enhance nuclear translocation of Nrf2 and increase expression of Nrf2-target antioxidant genes, including HO-1, NQO1, and UGT1A1
HO-1↑,
NQO1↑,
miR-155↓,
miR-200c↑,
SOX9↓,
*toxicity↓, broccoli sprout-infused beverage containing 400 μM glucoraphanin nightly for 2 weeks causing no adverse effects and being well tolerated in 200 subjects

1436- SFN,  PacT,  docx,    Sulforaphane enhances the anticancer activity of taxanes against triple negative breast cancer by killing cancer stem cells
- in-vivo, BC, SUM159
NF-kB↓, sulforaphane is capable of preferentially eliminating CSCs, by inhibiting NF-κB p65
ChemoSen↑, combination of docetaxel and sulforaphane exhibits a greater reduction in primary tumor volume
IL6↓, sulforaphane (2.5 μM and 5 μM) reduces the secretion of both IL-6 and IL-8 by 40–90%
IL8↑,

1434- SFN,  GEM,    Sulforaphane Potentiates Gemcitabine-Mediated Anti-Cancer Effects against Intrahepatic Cholangiocarcinoma by Inhibiting HDAC Activity
- in-vitro, CCA, HuCCT1 - in-vitro, CCA, HuH28 - in-vivo, NA, NA
HDAC↓,
ac‑H3↑,
ChemoSen↑, SFN synergistically augmented the GEM-mediated attenuation of cell viability and proliferation
tumCV↓,
TumCP↓,
TumCCA↑, G2/M cell cycle arrest
Apoptosis↑,
cl‑Casp3↑,
TumCI↓,
VEGF↓, VEGFA
VEGFR2↓,
Hif1a↓,
eNOS↓,
EMT?, SFN effectively inhibited the GEM-mediated induction of epithelial–mesenchymal transition (EMT)
TumCG↓,
Ki-67↓,
TUNEL↑, increased TUNEL+ apoptotic cells
P21↑,
p‑Chk2↑,
CDC25↓, decreased p-Cdc25C
BAX↑,
*ROS↓, SFN is also known to exert anti-oxidative effects via Nrf2 activation. in vivo study, optimization is performed by evaluating the anti-oxidative property of SFN in the liver.
NQO1?, identified 50 mg/kg/day as the minimal dose that significantly induced these anti-oxidative genes

1432- SFN,    Evaluation of biodistribution of sulforaphane after administration of oral broccoli sprout extract in melanoma patients with multiple atypical nevi
- Human, Melanoma, NA
other↑, Median skin sulforaphane levels on day 28 were 0.0 ng/g, 3.1 ng/g, and 34.1 ng/g for 50, 100, and 200 µmol, respectively
decorin↑,
*toxicity↓, Oral BSE-SFN is well-tolerated at daily doses up to 200 µmol and achieves dose-dependent levels in plasma and skin.
IP-10/CXCL-10↓,
MCP1↓,
CXCL9↓,
MIP-1β↓,
IFN-γ↓,

1431- SFN,    Induction of the phase 2 response in mouse and human skin by sulforaphane-containing broccoli sprout extracts
- in-vivo, Nor, NA
*NADPH↑, Topical application of an extract delivering 100 nmol sulforaphane/cm(2)
*NQO1↑,
*GSTA1↑,
*HO-1↑,

1430- SFN,    Sulforaphane bioavailability and chemopreventive activity in women scheduled for breast biopsy
- Trial, BC, NA
*HDAC3↓, HDAC3 (p = 0.044) levels significantly decreased in benign tissue
HDAC↓,
*toxicity↓, GFN supplementation for a few weeks is safe but may not be sufficient for producing changes in breast tissue tumor biomarkers.

1429- SFN,    Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast
- in-vivo, Nor, NA - Human, Nor, NA
*NADPH↑,
*NQO1↑, x3
*HO-1↑, x4
*Risk↑, strong rationale for evaluating the protective effects of a broccoli sprout preparation in clinical trials of women at risk for breast cancer.

1428- SFN,    Broccoli or Sulforaphane: Is It the Source or Dose That Matters?
- Review, NA, NA
HDAC↓, >100 µmol/kg
NRF2↑, sulforaphane is the most cited natural product activator of Nrf2 signaling

1315- SFN,    Sulforaphane Induces Apoptosis of Acute Human Leukemia Cells Through Modulation of Bax, Bcl-2 and Caspase-3
- in-vitro, AML, K562
TumCP↓,
BAX↑,
Casp3↑,
Bcl-2↓,

1136- SFN,    Sulforaphane inhibits epithelial-mesenchymal transition by activating extracellular signal-regulated kinase 5 in lung cancer cells
- in-vitro, Lung, NA - in-vivo, NA, NA
TumCMig↓,
E-cadherin↑,
ZO-1↑,
N-cadherin↓,
Snail↓, Snail1
ERK5↑,
EMT↓,

1061- SFN,    Relevance of the natural HDAC inhibitor sulforaphane as a chemopreventive agent in urologic tumors
- vitro+vivo, NA, NA
AntiTum↑,
HDAC↓, natural HDAC inhibitor sulforaphane

1014- SFN,    Sulforaphane Modulates Cell Migration and Expression of β-Catenin and Epithelial Mesenchymal Transition Markers in Breast Cancer Cells
- in-vitro, BC, MDA-MB-231
Zeb1↓,
Apoptosis↑,
Fibronectin↓,
CLDN1↓,
β-catenin/ZEB1↓, β-catenin revealed a time-dependent decrease at the concentration of 40 μM SFN
EMT↓,

963- SFN,    Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells
- in-vitro, CRC, HCT116 - in-vitro, GC, AGS
Hif1a↓,
VEGF↓,
angioG↓,
Akt∅, AKT and ERK signaling pathway is not involved in downregulation of HIF-1α protein by sulforaphane under hypoxic conditions
ERK∅,

111- SFN,    Sulforaphene Interferes with Human Breast Cancer Cell Migration and Invasion through Inhibition of Hedgehog Signaling
- in-vitro, BC, SUM159
HH↓,
Gli1↓,
MMP2↓,
MMP9↓,

1482- SFN,    Sulforaphane induces apoptosis in T24 human urinary bladder cancer cells through a reactive oxygen species-mediated mitochondrial pathway: the involvement of endoplasmic reticulum stress and the Nrf2 signaling pathway
- in-vitro, Bladder, T24
tumCV↓,
Apoptosis↑,
Cyt‑c↑,
Bax:Bcl2↑, Bcl-2/Bax dysregulation
Casp9↑,
Casp3↑,
Casp8∅,
cl‑PARP↑,
ROS↑, sulforaphane triggered reactive oxygen species (ROS) generation
MMP↓,
eff↓, blockage of sulforaphane-induced loss of mitochondrial membrane potential and apoptosis, was strongly attenuated by the ROS scavenger N-acetyl-L-cysteine.
ER Stress↑,
p‑NRF2↑, accumulation of phosphorylated Nrf2 proteins in the nucleus
HO-1↑, induction of heme oxygenase-1 expression

1509- SFN,    Combination therapy in combating cancer
- Review, NA, NA
NRF2↑, chemopreventive properties that are thought to be due to potent upregulation of Nrf2
ChemoSideEff↓, chemopreventive properties
eff↑, combined SFN with taxol in treatment of prostate cancer cell line DU145, and observed that SFN potentiated the effects of low doses of taxol
TumCP↓,
Apoptosis↑,
TumCCA↑, induce G2/M cell cycle arrest in vitro and in vivo
eff↑, SFN positively enhanced bortezomib, lenalidomide, and conventional drugs, such as dexamethasone, doxorubicin, and melphalan in a synergistic manner
PSA↓, SFN has shown to significantly reduce levels of prostate-specific antigen (PSA) (44.4% SFN group vs. 71.8% in placebo)
P53↑, SFN activates various anti-cancer responses such as p53, ARE, IRF-1, Pax-6 and XRE while suppressing proteins involved in tumorigenesis and progression, such as HIF1α, AP-1 and CA IX
Hif1a↓, while suppressing proteins involved in tumorigenesis and progression, such as HIF1α, AP-1 and CA IX
CAIX↓,
chemoR↓, SFN has thus shown to reduce chemoresistance and may be a potential agent to be used in conjunction with chemotherapeutics
5HT↓, SFN downregulates 5-HT receptor expression in Caco-2 cells

1508- SFN,    Nrf2 targeting by sulforaphane: A potential therapy for cancer treatment
- Review, Var, NA
*BioAv↑, RAW: higher amounts were detected when broccoli were eaten raw (bioavailability equal to 37%), compared to the cooked broccoli (bioavailability 3.4%)
HDAC↓, Sulforaphane is able to down-regulate HDAC activity and induce histone hyper-acetylation in tumor cell
TumCCA↓, Sulforaphane induces cell cycle arrest in G1, S and G2/M phases,
eff↓, in leukemia stem cells, sulforaphane potentiates imatinib effect through inhibition of the Wnt/β-catenin functions
Wnt↓,
β-catenin/ZEB1↓,
Casp12?, inducing caspases activation
Bcl-2↓,
cl‑PARP↑,
Bax:Bcl2↑, unbalancing the ratio Bax/Bcl-2
IAP1↓, down-regulating IAP family proteins
Casp3↑,
Casp9↑,
Telomerase↓, In Hep3B cells, sulforaphane reduces telomerase activity
hTERT↓, inhibition of hTERT expression;
ROS?, increment of ROS, induced by this compound, is essential for the downregulation of transcription and of post-translational modification of hTERT in suppression of telomerase activity
DNMTs↓, (2.5 - 10 μM) represses hTERT by impacting epigenetic pathways, in particular through decreased DNA methyltransferases activity (DNMTs)
angioG↓, inhibit tumor development through regulation of angiogenesis
VEGF↓,
Hif1a↓,
cMYB↓,
MMP1↓, inhibition of migration and invasion activities induced by sulforaphane in oral carcinoma cell lines has been associated to the inhibition of MMP-1 and MMP-2
MMP2↓,
MMP9↓,
ERK↑, inhibits invasion by activating ERK1/2, with consequent upregulation of E-cadherin (an invasion inhibitor)
E-cadherin↑,
CD44↓, downregulation of CD44v6 and MMP-2 (invasion promoters)
MMP2↓,
eff↑, ombination of sulforaphane and quercetin synergistically reduces the proliferation and migration of melanoma (B16F10) cells
IL2↑, induces upregulation of IL-2 and IFN-γ
IFN-γ↑,
IL1β↓, downregulation of IL-1beta, IL-6, TNF-α, and GM-CSF
IL6↓,
TNF-α↓,
NF-kB↓, sulforaphane inhibits the phorbol ester induction of NF-κB, inhibiting two pathways, ERK1/2 and NF-κB
ERK↓,
NRF2↑, At molecular level, sulforaphane modulates cellular homeostasis via the activation of the transcription factor Nrf2.
RadioS↑, sulforaphane could be used as a radio-sensitizing agent in prostate cancer if clinical trials will confirm the pre-clinical results.
ChemoSideEff↓, chemopreventive effects of sulforaphane

110- SFN,    Sulforaphane regulates self-renewal of pancreatic cancer stem cells through the modulation of Sonic hedgehog-GLI pathway
- in-vivo, PC, NA
HH↓,
Smo↓,
Gli1↓,
GLI2↓,
Shh↓,
VEGF↓,
PDGFRA↓,
EMT↓,
Zeb1↓,
Bcl-2↓,
XIAP↓,
E-cadherin↑,
OCT4↓,

1502- SFN,    Epigenetic targets of bioactive dietary components for cancer prevention and therapy
- Review, NA, NA
HDAC↓, (SFN), a major component present in cruciferous vegetables, inhibits HDAC activity
AntiCan↑, shown to reduce the risk of developing many common cancers
DNMTs↓, SFN was found to inhibit DNMTs in MCF-7 and MDA-MB-231 breast cancer as well as CaCo-2 colon cancer cells
hTERT↓, inhibited human telomerase reverse transcriptase (hTERT)
selectivity↑, inhibited (hTERT), in both MCF-7 and MDA-MB-231 human breast cancer cells and that it had negligible effects on normal control cells.

1501- SFN,    The Inhibitory Effect of Sulforaphane on Bladder Cancer Cell Depends on GSH Depletion-Induced by Nrf2 Translocation
- in-vitro, CRC, T24
Dose↝, SFN (2.5 µM) was shown to promote cell proliferation (5.18–11.84%) and migration in T24 cells, whilst high doses of SFN (>10 µM) inhibited cell growth significantly.
NRF2↑, induction effect of SFN on Nrf2 expression at both low (2.5 µM) and high dose (10 µM) was characterized by a bell-shaped curve.
GSH↓, highly dependent on Nrf2-mediated GSH depletion and following production. These findings suggested that a higher dose of SFN is required for the prevention and treatment of bladder cancer.
eff↑, GSH-depleting agent L-Buthionine-sulfoximine abolished the effect of SFN on cell proliferation.

1500- SFN,    A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase
- in-vitro, Nor, HEK293 - in-vitro, CRC, HCT116
HDAC↓, SFN dose-dependently increased TOPflash reporter activity and inhibited HDAC activity
P21↑,
TOPflash↑, increased TOPflash reporter activity

1499- SFN,    Sulforaphane suppresses metastasis of triple-negative breast cancer cells by targeting the RAF/MEK/ERK pathway
- in-vitro, BC, NA
TumCMig↓, significantly inhibited TGF-β1-induced migration and invasion in breast cancer cells
TumCI↓,
FAK↓,
p‑MEK↓, SFN is directly bound to RAF family proteins (including ARAF, BRAF, and CRAF) and inhibited MEK and ERK phosphorylation
p‑ERK↓,

1498- SFN,    Prolonged sulforaphane treatment activates survival signaling in nontumorigenic NCM460 colon cells but apoptotic signaling in tumorigenic HCT116 colon cells
- in-vitro, CRC, HCT116 - in-vitro, Nor, NCM460
selectivity↑, we demonstrated that SFN (15 μmol/L) exposure (72 h) inhibited cell proliferation by up to 95% in colon cancer cells (HCT116) and by 52% in normal colon mucosa-derived (NCM460) cells
TumCCA↑, reduction of G1 phase cell distribution
Apoptosis↑, apoptosis in HCT116 cells, but to a much lesser extent in NCM460 cells
*p‑ERK↑, in NCM460 cells but not in HCT116 cells
cMYB↓, decreased c-Myc expression in HCT116 cells but not NCM460 cells.
selectivity↑, decreased c-Myc expression in HCT116 cells but not NCM460 cells.
selectivity↑, upregulated p-ERK1/2 in NCM460 cells but not in HCT116 cells

1497- SFN,    Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells
- in-vitro, Nor, PrEC - in-vitro, Pca, LNCaP - in-vitro, Pca, PC3
HDAC↓, ability of SFN to inhibit histone deacetylase enzymes
selectivity↑, 15 µM SFN selectively induced cell cycle arrest and apoptosis in BPH1, LnCap and PC3 cells but not PrEC cells
TumCCA↑,
Apoptosis↑,
selectivity↑, selectively decreased HDAC activity
H3↑,
P21↑, in prostate cancer cells
selectivity↑, we conclude that SFN exerts differential effects on cell proliferation, HDAC activity and downstream targets in normal and cancer cells.

1496- SFN,  VitD3,    Association between histone deacetylase activity and vitamin D-dependent gene expressions in relation to sulforaphane in human colorectal cancer cells
- in-vitro, CRC, Caco-2
eff↑, data suggest that colon cancer cells respond to dietary components differently under different conditions.
VDR↑, in proliferating Caco-2 cells, D + SFN (P < 0.04) increased VDR expression and decreased CYP27B1
CYP11A1↓,
HDAC↓, Histone deacetylase (HDAC) inhibitor activity was assessed using HDAC I/II assay that measured global changes in acetylation status.

1495- SFN,  doxoR,    Sulforaphane protection against the development of doxorubicin-induced chronic heart failure is associated with Nrf2 Upregulation
- in-vivo, Nor, NA
*CardioT↓, SFN significantly prevented DOX-induced progressive cardiac dysfunction between 2-6 weeks and prevented DOX-induced cardiac function deterioration.
*NRF2↑, SFN upregulated NF-E2-related factor 2 (Nrf2)
*eff↓, protective effect of SFN against DOX-induced fibrotic and inflammatory responses was abolished by Nrf2 silencing.
*ROS↓, prevented DOX-induced cardiac oxidative stress

1494- SFN,  doxoR,    Sulforaphane potentiates anticancer effects of doxorubicin and attenuates its cardiotoxicity in a breast cancer model
- in-vivo, BC, NA - in-vitro, BC, MCF-7 - in-vitro, Nor, MCF10
CardioT↓, SFN (4 mg/kg, 5 days/week) protected against mortality and cardiac dysfunction induced by DOX
*GSH↑, Rats Hearts: SFN and DOX co-treatment reduced MDA and 4-HNE adduct formation and also prevented DOX-induced depletion of GSH levels
*ROS↓, SFN reduces DOX-induced oxidative stress in the heart of non-tumor bearing rats.
*NRF2↑, activates Nrf2 in rat hearts during DOX treatment
NRF2∅, SFN does not interfere with DOX toxicity or Nrf2 activity in breast cancer cell lines
HDAC↓, SFN acts synergistically with DOX to inhibit HDAC and DNMT activity, decrease ERα detection and increase caspase-3 activity
DNMTs↓,
Casp3↑,
ER-α36↓, ERα levels in MCF-7, MDA-MB-231
Remission↑, SFN+DOX treatment (with a total DOX dose of 20 mg/kg) was able to eradicate the tumors in all rats by day 35 after tumor implantation
eff↑, SFN (4 mg/kg oral; 5 days/week for 5 weeks) with DOX (total of 10 or 20 mg/kg i.p. administered over 4 weeks) and showed that in combination with SFN, the dosage of DOX could be < by 50% while still eliciting the same anti-cancer effects as DOX alone
ROS↑, Increased generation of reactive oxygen species (ROS), an altered redox status, and aerobic glycolysis for energy production distinguish highly proliferative cancer cells from normal healthy cells
selectivity?, ROS production... distinguish highly proliferative cancer cells from normal healthy cells

1484- SFN,    Sulforaphane’s Multifaceted Potential: From Neuroprotection to Anticancer Action
- Review, Var, NA - Review, AD, NA
neuroP↑, current evidence supporting the neuroprotective and anticancer effects of SFN
AntiCan↑,
NRF2↑, neuroprotective effects through the activation of the Nrf2 pathway
HDAC↓, histone deacetylase was inhibited after human subjects ingested 68 g of broccoli sprouts
eff↑, sensitize cancer cells to chemotherapy
*ROS↓, protecting neurons [14] and microglia [15] against oxidative stress
neuroP↑, neuroprotective effects in Alzheimer’s disease (AD)
HDAC↓, capacity as a histone deacetylase (HDAC) inhibitor
*toxicity∅, normal cells are relatively resistant to SFN-induced cell death
BioAv↑, SFN has good bioavailability; it can reach high intracellular and plasma concentrations
eff↓, However, it is important to consider that at lower doses, specifically 2.5 μM, SFN resulted in a slight increase in cell proliferation by 5.18–11.84% within a 6 to 48 h treatment window
cycD1↓, in breast cancer
CDK4↓, in breast cancer
p‑RB1↓, in breast cancer
Glycolysis↓, in prostate cancer
miR-30a-5p↑, ovarian cancer
TumCCA↑, gastric cancer
TumCG↓,
TumMeta↓,
eff↑, SFN emerged as a critical enhancer of ST’s efficacy by suppressing resistance in RCC cells, offering a potent approach to overcome ST monotherapy limitations.
ChemoSen↑, SFN may improve the effectiveness of chemotherapy by increasing cancer cell sensitivity to the drugs used to treat them
RadioS↑, SFN may help protect healthy cells and tissues from the harmful effects of radiation
CardioT↓, Several studies have demonstrated the protective role of SFN in cardiotoxicity
angioG↓, In colon cancers, SFN blocks cells’ progression and angiogenesis by inhibiting HIF-1α and VEGF expression
Hif1a↓,
VEGF↓,
*BioAv?, SFN is well absorbed in the intestine, with an absolute bioavailability of approximately 82%.
*Half-Life∅, In rats, after an oral dose of 50 μmol of SFN, the plasma concentration of SFN can peak at 20 μM at 4 h and decline with a half-life of about 2.2 h

1483- SFN,    Targeting p62 by sulforaphane promotes autolysosomal degradation of SLC7A11, inducing ferroptosis for osteosarcoma treatment
- in-vitro, OS, 143B - in-vitro, Nor, HEK293 - in-vivo, OS, NA
AntiCan↑, has shown potential anti-cancer effects with negligible toxicity
*toxicity∅, (liver, kidney, heart, spleen, and lung) showed no evidence of toxicity associated with SFN treatment
Ferroptosis↑, results demonstrate the dependency of downregulation of SLC7A11 in SFN-induced ferroptosis in OS cells
ROS↑, elevated ROS levels, lipid peroxidation, and GSH depletion
lipid-P↑,
GSH↓, which was dependent on decreased levels of SLC7A11
p62↑, enhanced p62/SLC7A11 protein-protein interaction, thereby promoting the lysosomal degradation of SLC7A11 and triggering ferroptosis
SLC12A5↓, SFN induces ferroptosis of OS cells through downregulation of SLC7A11
eff↓, ferroptosis inhibitors Fer-1 (ferrostatin-1), DFO (deferoxamine), and Lip-1 (liproxstatin-1) substantially rescued the cells from SFN-induced cell death
GPx4↓, SFN treatment markedly reduced the expression levels of ferroptosis markers GPX4 and SLC7A11 in OS cells
i-Iron↑, validated the intracellular Fe2+ accumulation by SFN
eff↓, SLC7A11 overexpression notably reversed SFN-induced changes in the ROS level, GSH level, and lipid peroxidation
MDA↑, SFN treatment reduced GSH levels and increased MDA production, indicating the induction of ferroptosis
TumVol↓,
TumW↓,
Ki-67↓, subcutaneous tumors revealed significantly lower expression levels of Ki67, SLC7A11, and GPX4, along with upregulated LC3B in the SFN-treated group
LC3B↑,
*Weight∅, no significant difference in body weight was observed between the control and SFN-treated groups

1513- SFN,  acetaz,    Next-generation multimodality of nutrigenomic cancer therapy: sulforaphane in combination with acetazolamide actively target bronchial carcinoid cancer in disabling the PI3K/Akt/mTOR survival pathway and inducing apoptosis
- in-vitro, BrCC, H720 - in-vivo, BrCC, NA - in-vitro, BrCC, H727
eff↑, Combining AZ+SFN reduced tumor cell survival compared to each agent alone, both in vitro and in vivo xenograft tissues.
tumCV↓,
Apoptosis↑,
P21↑,
PI3K↓,
Akt↓,
mTOR↓,
5HT↓, significantly reducing 5-HT secretion in carcinoid syndrome.
NRF2↑, AZ and SFN increased the expression of Nrf2 by 61% and 104%, respectively. Combination treatment further increased expression by 127%

1481- SFN,  docx,    Combination of Low-Dose Sulforaphane and Docetaxel on Mitochondrial Function and Metabolic Reprogramming in Prostate Cancer Cell Lines
- in-vitro, Pca, LNCaP - in-vitro, Pca, PC3
ChemoSen↑, SFN:DCT combination reduced cell viability to 50%
Casp3↑,
ROS↑, see figure 4
Casp8↑,
Cyt‑c↑, see figure 4
Glycolysis↓, see figure 4
GSH↓, see figure 4
GSH/GSSG↓, GSH/GSSG
*toxicity↓, SFN:DCT combination, administered at reduced doses, not only preserves efficacy but also minimizes toxicity

1480- SFN,    Sulforaphane Induces Cell Death Through G2/M Phase Arrest and Triggers Apoptosis in HCT 116 Human Colon Cancer Cells
- in-vitro, CRC, HCT116
tumCV↓,
TumCCA↑, G2/M phase arrest
Apoptosis↑,
cycA1↑,
CycB↑,
CDC25↓, Cdc 25C
CDK1↓,
ROS↑, SFN induced the generation of reactive oxygen species (ROS)
eff↓, Ca[Formula: see text] and decreased mitochondria membrane potential and increased caspase-8, -9 and -3 activities in HCT 116 cell
Cyt‑c↑,
AIF↑,
ER Stress↑,

1479- SFN,    Sulforaphane triggers Sirtuin 3-mediated ferroptosis in colorectal cancer cells via activating the adenosine 5'-monophosphate (AMP)-activated protein kinase/ mechanistic target of rapamycin signaling pathway
- in-vitro, CRC, HCT116
Ferroptosis↑, sulforaphane triggered the ferroptosis of HCT-116 cells by activating the SIRT3/AMPK/mTOR axis
SIRT3↑,
AMPK↑,
mTOR↑,
tumCV↓, SIRT3 overexpression reduced cell viability and increased intracellular levels of ROS, MDA, and iron
ROS↑,
MDA↑,
Iron↑,

1478- SFN,  acet,    Anti-inflammatory and anti-oxidant effects of combination between sulforaphane and acetaminophen in LPS-stimulated RAW 264.7 macrophage cells
- in-vitro, Nor, NA
eff↑, combination of SFN and APAP exhibited an inhibitory effect on inflammatory markers such as NO, iNOS, COX-2, and IL-1β, and this effect was more pronounced than the compound was used alone.
NO↓,
iNOS↓,
COX2↓,
IL1β↓,
ROS↓, combination of SFN and APAP at LOW doses decreased intracellular ROS formation

1477- SFN,    Sulforaphane Induces Oxidative Stress and Death by p53-Independent Mechanism: Implication of Impaired Glutathione Recycling
- in-vitro, OS, MG63
tumCV↓,
Apoptosis↑,
Casp3↑,
ROS↑, >=10 μM, At these higher doses, SFN increased ROS levels
GSR↓, inhibition of glutathione reductase
GPx↓,

1476- SFN,  PDT,    Enhancement of cytotoxic effect on human head and neck cancer cells by combination of photodynamic therapy and sulforaphane
- in-vitro, HNSCC, NA
eff↑, Cell viability was decreased significantly by combination treatment
tumCV↓,
ROS↑, ROS generation was also higher in combination treatment
eff↓, In combination treatment group, apoptosis and necrosis were decreased by administration of sodium azide (SA) which is scavenger of ROS.
Casp↑,

1475- SFN,  Form,    Combination of Formononetin and Sulforaphane Natural Drug Repress the Proliferation of Cervical Cancer Cells via Impeding PI3K/AKT/mTOR Pathway
- in-vitro, Cerv, HeLa
TumCP↓,
PI3K↓,
Akt↓,
mTOR↓,
eff↑, cytotoxicity of FN and SFN was determined to be around 23.7 µM and 26.92 µM, respectively. Combining FN and SFN causes considerable cytotoxicity in HeLa cells, with an IC50 of 21.6 µM
ROS↑, considerable ROS generation

1474- SFN,    Sulforaphane induces p53‑deficient SW480 cell apoptosis via the ROS‑MAPK signaling pathway
- in-vitro, Colon, SW480
TumCG↓,
Apoptosis↑,
MMP↓,
Bax:Bcl2↑,
Casp3↑,
Casp7↑,
Casp9↑,
ROS↑, increase in the generation of reactive oxygen species (ROS)
e-ERK↑, activation of extracellular signal‑regulated kinases (Erk)
p38↑,
P53∅,
eff↓, specific inhibitors for ROS, phosphorylated (p)‑Erk and p‑p38, completely or partially attenuated the SFN‑induced reduction in SW480 cell viability
ChemoSen↑, even at the lowest concentrations (5 µM), SFN increased the sensitivity of p53‑proficient HCT‑116 cells to cisplatin

1472- SFN,    Sulforaphane Inhibits Autophagy and Induces Exosome-Mediated Paracrine Senescence via Regulating mTOR/TFE3
- in-vitro, ESCC, NA
TumCP↓,
ROS↑, SFN induces reactive oxygen species (ROS) via disrupting the balance between glutathione and oxidized glutathione, leading to DNA damage.
DNAdam↑,

1471- SFN,    ROS-mediated activation of AMPK plays a critical role in sulforaphane-induced apoptosis and mitotic arrest in AGS human gastric cancer cells
- in-vitro, GC, AGS
TumCP↓,
Apoptosis↑,
TumCCA↑, G2/M phase
CycB↑,
P21↑,
p‑H3↑,
p‑AMPK↑,
eff↓, compound C, an AMPK inhibitor, significantly blocked sulforaphane-induced apoptosis
MMP↓,
Cyt‑c↑,
ROS↑, sulforaphane provoked the generation of intracellular ROS
eff↓, sulforaphane provoked the generation of intracellular ROS; especially when ROS production was blocked by antioxidant N-acetylcysteine, both AMPK activation and growth inhibition by sulforaphane were completely abolished

1470- SFN,  Rad,    Sulforaphane induces ROS mediated induction of NKG2D ligands in human cancer cell lines and enhances susceptibility to NK cell mediated lysis
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, Lung, A549 - in-vitro, lymphoma, U937
eff↓, NK cell mediated killing was abrogated by N-acetyl cysteine in A549 and MDA-MB-231 cells suggesting a ROS mediated mechanism.
ROS↑,
NKG2D↑, ability to up-regulate natural killer group 2, member D (NKG2D) ligands and modulate the susceptibility of tumor cells to natural killer (NK) cell-mediated killing.

1469- SFN,    Sulforaphane enhances the therapeutic potential of TRAIL in prostate cancer orthotopic model through regulation of apoptosis, metastasis, and angiogenesis
- in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP - in-vivo, Pca, NA
eff↑, Sulforaphane enhanced the therapeutic potential of TRAIL in PC-3 cells and sensitized TRAIL-resistant LNCaP cells.
ROS↑,
MMP↓,
Casp3↑,
Casp9↑,
DR4↑,
DR5↑,
BAX↑,
Bak↑,
BIM↑,
NOXA↑,
Bcl-2↓,
Bcl-xL↓,
Mcl-1↓,
eff↓, quenching of ROS generation with antioxidant N-acetyl-L-cysteine conferred significant protection against sulforaphane-induced ROS generation, mitochondrial membrane potential disruption, caspase-3 activation, and apoptosis.
TumCG↓,
TumCP↓,
eff↑, enhanced the antitumor activity of TRAIL.
NF-kB↓,
PI3K↓,
Akt↓,
MEK↓,
ERK↓,
angioG↓, combination of sulforaphane and TRAIL was more effective in inhibiting markers of angiogenesis and metastasis and activating FOXO3a transcription factor than single agent alone.
FOXO3↑,

1468- SFN,    Cellular responses to dietary cancer chemopreventive agent D,L-sulforaphane in human prostate cancer cells are initiated by mitochondrial reactive oxygen species
- in-vitro, Pca, LNCaP - in-vitro, Pca, PC3
ROS↑,
DNAdam↑,
MMP↓,
Cyt‑c↑,
TumCCA↑, G2/M phase cell cycle arrest


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 125

Results for Effect on Cancer/Diseased Cells:
5HT↓,2,   ACC↓,1,   ACC1↓,1,   AIF↑,2,   Akt↓,6,   Akt∅,1,   p‑Akt↓,3,   AKT1↓,2,   ALDH↓,1,   ALDH1A1↓,2,   AMPK↑,3,   p‑AMPK↑,1,   angioG↓,9,   AntiCan↑,6,   antiOx↓,1,   antiOx↑,3,   AntiTum↑,1,   AP-1↓,2,   Apoptosis↑,30,   AQPs↓,1,   AR↓,2,   ATP↓,3,   Bak↑,1,   BAX↑,9,   Bax:Bcl2↑,5,   Bcl-2↓,9,   Bcl-2∅,1,   Bcl-xL↓,2,   BID↑,2,   BIM↑,1,   BioAv↓,2,   BioAv↑,5,   BioAv↝,2,   BMI1↓,1,   Ca+2↑,1,   CAIX↓,1,   cal2↑,1,   cardioP↑,1,   CardioT↓,2,   Casp↑,3,   Casp12?,1,   Casp12↑,2,   Casp3↑,19,   cl‑Casp3↑,2,   Casp7↑,4,   Casp8↑,6,   Casp8∅,2,   Casp9↑,11,   Catalase↑,1,   CD133↓,2,   CD44↓,4,   CDC25↓,2,   CDK1↓,1,   CDK1↑,2,   p‑CDK1↑,1,   CDK2↓,1,   CDK2↑,1,   CDK4↓,3,   CDK6↓,1,   chemoP↑,6,   chemoR↓,1,   ChemoSen↑,12,   ChemoSideEff↓,3,   p‑Chk2↑,1,   CHOP↑,1,   CLDN1↓,1,   cMYB↓,2,   cMyc↓,2,   COMT↑,1,   COX2↓,5,   COX2↝,1,   CPT1A↓,1,   CSCs↓,9,   CXCL9↓,1,   CXCR4↓,2,   cycA1↓,1,   cycA1↑,1,   CycB↓,1,   CycB↑,3,   cycD1↓,2,   cycD1↑,2,   cycE↓,1,   CYP11A1↓,1,   CYP1A1↓,2,   CYP3A4↓,1,   Cyt‑c↓,1,   Cyt‑c↑,12,   decorin↑,1,   Diablo↑,2,   Diff↓,1,   DNAdam↓,1,   DNAdam↑,5,   DNArepair↓,1,   DNMT1↓,5,   DNMT3A↓,4,   DNMTs↓,8,   Dose↝,8,   Dose∅,1,   DR4↑,1,   DR5↑,3,   E-cadherin↓,1,   E-cadherin↑,5,   ECAR↓,2,   eff↓,26,   eff↑,28,   eff↝,2,   EGFR↓,3,   EMT?,1,   EMT↓,9,   eNOS↓,1,   ER Stress↑,4,   ER-α36↓,1,   ERK↓,4,   ERK↑,2,   ERK∅,1,   p‑ERK↓,1,   e-ERK↑,1,   ERK5↑,1,   EZH2↓,1,   FAK↓,1,   Fas↑,1,   FASN↓,2,   Ferroptosis↑,2,   Fibronectin↓,1,   FOXO3↑,1,   Gli↓,1,   Gli1↓,6,   GLI2↓,3,   glucoNG↓,1,   GlucoseCon↓,1,   Glycolysis↓,11,   GPx↓,1,   GPx4↓,1,   GRP78/BiP↑,2,   GSH↓,6,   GSH↑,2,   GSH/GSSG↓,1,   GSR↓,1,   GSTA1↑,1,   GSTs↑,1,   GutMicro↝,1,   H3↓,1,   H3↑,2,   p‑H3↑,1,   ac‑H3↑,2,   H4↑,1,   ac‑H4↑,1,   Half-Life∅,1,   HATs↓,1,   HDAC↓,30,   HDAC↑,1,   HDAC1↓,1,   HDAC2↓,2,   HDAC3↓,3,   HDAC4↓,1,   HDAC8↓,2,   HER2/EBBR2↓,2,   HH↓,2,   Hif1a↓,14,   HK2↓,7,   HMTs↓,1,   HO-1↑,6,   HSP27↑,1,   HSP70/HSPA5↓,1,   HSP90↓,1,   ac‑HSP90↑,1,   hTERT↓,5,   IAP1↓,1,   IAP1↑,1,   ICAD↑,1,   IFN-γ↓,1,   IFN-γ↑,1,   IGF-1↓,1,   IKKα↓,1,   IL12↓,1,   IL1β↓,4,   IL2↑,1,   IL6↓,4,   IL8↑,1,   Inflam↓,3,   iNOS↓,1,   IP-10/CXCL-10↓,1,   Iron↑,1,   i-Iron↑,1,   JAK2↓,1,   Ki-67↓,2,   KIF2C↓,1,   KLF4↓,1,   lactateProd↓,1,   LAMP1?,1,   LAMP2↑,1,   LC3B↑,1,   LC3II↑,1,   LDHA↓,3,   lipid-P↑,1,   MAPK↑,1,   Mcl-1↓,1,   MCP1↓,1,   MDA↑,2,   MEK↓,1,   p‑MEK↓,1,   Mets↑,1,   MIP-1β↓,1,   miR-155↓,1,   miR-200c↑,1,   miR-30a-5p↑,1,   MMP↓,14,   MMP1↓,1,   MMP13↓,1,   MMP2↓,10,   MMP2↝,1,   MMP9↓,10,   MMP9↝,1,   MMPs↓,1,   MPO↓,1,   mTOR↓,3,   mTOR↑,1,   p‑mTOR↓,1,   N-cadherin↓,2,   NA↑,1,   NAD↑,1,   Nanog↓,6,   Nestin↓,1,   neuroP↑,4,   NF-kB↓,11,   NKG2D↑,1,   NO↓,1,   NO↑,1,   NOTCH↓,1,   NOTCH1↓,1,   NOX↓,1,   NOXA↑,1,   NQO1?,1,   NQO1↑,3,   NRF2↑,15,   NRF2∅,1,   p‑NRF2↑,1,   OCT4↓,4,   OS↑,2,   OS∅,1,   other↓,1,   other↑,2,   OXPHOS↓,1,   mt-OXPHOS↓,1,   p19↑,2,   P21↑,11,   p27↑,2,   p38↓,2,   p38↑,3,   P450↓,1,   p50↓,1,   P53↑,3,   P53∅,1,   p62↑,1,   p70S6↓,1,   cl‑PARP↑,9,   p‑PDGF↓,1,   PDGFRA↓,2,   PDH↓,1,   PI3K↓,6,   PKA↓,1,   PKM2↓,5,   Prot↝,1,   Prx↓,2,   PSA↓,2,   PUMA↑,1,   RadioS↑,3,   p‑RB1↓,1,   Remission↑,1,   RenoP↑,1,   Risk↓,2,   ROS?,1,   ROS↓,4,   ROS↑,32,   ROS⇅,2,   selectivity?,1,   selectivity↓,1,   selectivity↑,12,   Shh↓,5,   SIRT3↑,1,   SLC12A5↓,1,   Slug↓,2,   Smad1↑,1,   Smo↓,5,   Snail↓,7,   SOD↑,1,   SOX2↓,1,   SOX9↓,1,   Sp1/3/4↓,1,   SREBP1?,1,   SREBP1↓,1,   p‑STAT3↓,1,   survivin↓,4,   TBX15↑,1,   TCF↓,1,   Telomerase↓,1,   TFEB↑,1,   TNF-α↓,4,   TOPflash↑,1,   TRAIL↑,1,   TrxR↓,1,   TrxR1↓,1,   TumAuto↑,2,   TumCCA?,1,   TumCCA↓,1,   TumCCA↑,22,   TumCD↑,1,   TumCG↓,12,   TumCI↓,9,   TumCMig↓,6,   TumCP↓,18,   tumCV↓,12,   TumMeta↓,4,   TumVol↓,1,   TumW↓,3,   TUNEL↑,1,   Twist↓,2,   UPR↑,1,   VCAM-1↓,1,   VDR↑,1,   VEGF↓,10,   VEGFR2↓,2,   Vim↓,1,   Warburg↓,1,   Wnt↓,4,   XBP-1↑,1,   XIAP↓,3,   Zeb1↓,7,   ZO-1↑,1,   β-catenin/ZEB1↓,5,   β-oxidation↓,1,   γH2AX↑,2,  
Total Targets: 332

Results for Effect on Normal Cells:
ACC↑,1,   ALAT↓,2,   AMPK↑,1,   ASC↓,1,   AST↓,2,   BioAv?,1,   BioAv↓,3,   BioAv↑,8,   BioAv↝,5,   cardioP↑,2,   CardioT↓,1,   Casp1↓,1,   Catalase↓,1,   Catalase↑,1,   cognitive↑,2,   Cyt‑c↓,1,   Dose↝,1,   eff↓,1,   eff↑,3,   ER Stress↓,1,   ERK↓,1,   p‑ERK↑,1,   Fibronectin↓,1,   G6PD↑,1,   GlucoseCon↓,1,   GPx↑,2,   GSH↑,2,   GSTA1↑,2,   Half-Life∅,2,   HDAC↓,2,   HDAC3↓,2,   hepatoP↑,1,   HK2↓,1,   HO-1↑,4,   HSP27↓,1,   IAP1↓,1,   ICAM-1↓,1,   p‑IKKα↓,1,   IL18↓,1,   IL1β↓,4,   IL6↓,5,   IL8↓,3,   Inflam↓,5,   ITGA5↓,1,   ITGB1↓,1,   Ki-67↓,1,   LDH↓,1,   M1↓,1,   memory↑,1,   mTOR↓,1,   NADPH↑,3,   NF-kB↓,1,   NLRP3↓,2,   NO↓,1,   NOS2↓,1,   NQO1↑,5,   NRF2↑,10,   OXPHOS↑,1,   P70S6K↓,1,   PFKFB2↓,1,   Rho↓,1,   Risk↑,1,   ROCK1↓,1,   ROS↓,9,   SOD↑,1,   TNF-α↓,1,   toxicity↓,8,   toxicity∅,4,   Trx↓,1,   TXNIP↑,1,   Weight∅,1,   α-SMA↓,1,  
Total Targets: 72

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:156  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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