condition found tbRes List
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↓">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↓, 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


ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK: regulates energy metabolism and can increase ROS levels when activated.
• mTOR: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Melavonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day
-Dipyridamole typically 200mg 2x/day
-Lycopene typically 100mg/day range

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

Scientific Papers found: Click to Expand⟱
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↑,

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↑,

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.

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↓,

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

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

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,

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.

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.

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

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

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.

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

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

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

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

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: 45

Results for Effect on Cancer/Diseased Cells:
AIF↑,2,   Akt↓,3,   p‑Akt↓,2,   AKT1↓,1,   ALDH↓,1,   ALDH1A1↓,1,   AMPK↑,2,   p‑AMPK↑,1,   angioG↓,5,   AntiCan↑,4,   antiOx↓,1,   AP-1↓,2,   Apoptosis↑,18,   AQPs↓,1,   ATP↓,1,   Bak↑,1,   BAX↑,7,   Bax:Bcl2↑,4,   Bcl-2↓,4,   Bcl-2∅,1,   Bcl-xL↓,1,   BID↑,1,   BIM↑,1,   BioAv↓,1,   BioAv↑,2,   BioAv↝,2,   cardioP↑,1,   CardioT↓,2,   Casp↑,2,   Casp12?,1,   Casp3↑,14,   cl‑Casp3↑,2,   Casp7↑,2,   Casp8↑,4,   Casp8∅,2,   Casp9↑,9,   Catalase↑,1,   CD133↓,1,   CD44↓,3,   CDC25↓,2,   CDK1↓,1,   CDK1↑,1,   p‑CDK1↑,1,   CDK4↓,1,   chemoP↑,4,   ChemoSen↑,10,   ChemoSideEff↓,1,   p‑Chk2↑,1,   cMYB↓,1,   COX2↓,3,   CSCs↓,1,   cycA1↑,1,   CycB↑,3,   cycD1↓,1,   cycD1↑,1,   CYP1A1↓,1,   CYP3A4↓,1,   Cyt‑c↓,1,   Cyt‑c↑,9,   DNAdam↑,4,   DNMT1↓,1,   DNMT3A↓,1,   DNMTs↓,2,   Dose↝,1,   DR4↑,1,   DR5↑,3,   E-cadherin↑,1,   eff↓,24,   eff↑,13,   EGFR↓,3,   EMT?,1,   EMT↓,3,   eNOS↓,1,   ER Stress↑,3,   ER-α36↓,1,   ERK↓,4,   ERK↑,2,   e-ERK↑,1,   Ferroptosis↑,2,   FOXO3↑,1,   Gli1↓,1,   glucoNG↓,1,   Glycolysis↓,4,   GPx↓,1,   GPx4↓,1,   GSH↓,4,   GSH/GSSG↓,1,   GSR↓,1,   GSTA1↑,1,   GutMicro↝,1,   p‑H3↑,1,   ac‑H3↑,1,   HATs↓,1,   HDAC↓,11,   HER2/EBBR2↓,2,   Hif1a↓,5,   HK2↓,1,   HO-1↑,3,   hTERT↓,2,   IAP1↓,1,   IFN-γ↑,1,   IL1β↓,3,   IL2↑,1,   IL6↓,2,   Inflam↓,2,   iNOS↓,1,   Iron↑,1,   i-Iron↑,1,   JAK2↓,1,   Ki-67↓,2,   LAMP1?,1,   LC3B↑,1,   LC3II↑,1,   lipid-P↑,1,   MAPK↑,1,   Mcl-1↓,1,   MDA↑,2,   MEK↓,1,   Mets↑,1,   miR-30a-5p↑,1,   MMP↓,13,   MMP1↓,1,   MMP2↓,5,   MMP9↓,5,   mTOR↓,1,   mTOR↑,1,   p‑mTOR↓,1,   NAD↑,1,   Nanog↓,1,   neuroP↑,3,   NF-kB↓,6,   NKG2D↑,1,   NO↓,1,   NOTCH↓,1,   NOX↓,1,   NOXA↑,1,   NQO1?,1,   NRF2↑,6,   NRF2∅,1,   p‑NRF2↑,1,   OCT4↓,1,   other↑,1,   mt-OXPHOS↓,1,   p19↑,1,   P21↑,5,   p27↑,1,   p38↓,2,   p38↑,2,   P450↓,1,   P53↑,1,   P53∅,1,   p62↑,1,   p70S6↓,1,   cl‑PARP↑,8,   PI3K↓,3,   Prx↓,2,   RadioS↑,3,   p‑RB1↓,1,   Remission↑,1,   ROS?,1,   ROS↓,4,   ROS↑,32,   ROS⇅,2,   selectivity?,1,   selectivity↑,1,   Shh↓,1,   SIRT3↑,1,   SLC12A5↓,1,   Slug↓,1,   Smo↓,1,   Snail↓,1,   p‑STAT3↓,1,   survivin↓,1,   Telomerase↓,1,   TFEB↑,1,   TNF-α↓,2,   TRAIL↑,1,   TrxR↓,1,   TrxR1↓,1,   TumAuto↑,1,   TumCCA?,1,   TumCCA↓,1,   TumCCA↑,13,   TumCG↓,7,   TumCI↓,5,   TumCMig↓,1,   TumCP↓,8,   tumCV↓,9,   TumMeta↓,3,   TumVol↓,1,   TumW↓,3,   TUNEL↑,1,   Twist↓,1,   VEGF↓,3,   VEGFR2↓,1,   Wnt↓,2,   Zeb1↓,1,   β-catenin/ZEB1↓,1,   γH2AX↑,2,  
Total Targets: 199

Results for Effect on Normal Cells:
ACC↑,1,   ALAT↓,1,   AST↓,1,   BioAv?,1,   BioAv↑,2,   BioAv↝,4,   cardioP↑,1,   CardioT↓,1,   Catalase↓,1,   Catalase↑,1,   cognitive↑,1,   Dose↝,1,   eff↓,1,   G6PD↑,1,   GlucoseCon↓,1,   GPx↑,2,   GSH↑,2,   Half-Life∅,1,   HDAC↓,1,   HDAC3↓,1,   hepatoP↑,1,   HK2↓,1,   HO-1↑,2,   IL1β↓,1,   IL6↓,2,   Inflam↓,2,   Ki-67↓,1,   LDH↓,1,   M1↓,1,   memory↑,1,   NADPH↑,1,   NF-kB↓,1,   NO↓,1,   NOS2↓,1,   NQO1↑,2,   NRF2↑,8,   OXPHOS↑,1,   PFKFB2↓,1,   ROS↓,9,   SOD↑,1,   TNF-α↓,1,   toxicity↓,3,   toxicity∅,3,   Trx↓,1,   TXNIP↑,1,   Weight∅,1,  
Total Targets: 46

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
45 Sulforaphane (mainly Broccoli)
2 doxorubicin
1 Biochanin A
1 Chemotherapy
1 Auranofin
1 Gemcitabine (Gemzar)
1 Docetaxel
1 acetaminophen
1 Photodynamic Therapy
1 Formononetin
1 Radiotherapy/Radiation
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:156  Target#:275  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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