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↓, 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


angioG, angiogenesis: Click to Expand ⟱
Source:
Type:
Process through which new blood vessels.
Angiogenesis, the process of new blood vessel formation from pre-existing vessels, plays a crucial role in cancer progression and metastasis. Tumors require a blood supply to grow beyond a certain size and to spread to other parts of the body.
Vascular Endothelial Growth Factor (VEGF): VEGF is one of the most important pro-angiogenic factors. It stimulates endothelial cell proliferation and migration, leading to the formation of new blood vessels. Many tumors overexpress VEGF, which correlates with poor prognosis.
Hypoxia-Inducible Factor (HIF): In response to low oxygen levels (hypoxia), tumors can activate HIF, which in turn promotes the expression of VEGF and other angiogenic factors. This mechanism allows tumors to adapt to their microenvironment and sustain growth.
Scientific Papers found: Click to Expand⟱
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)

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↓,

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,

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).

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

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∅,

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

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

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↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   Akt∅,1,   p‑Akt↓,1,   angioG↓,9,   AntiCan↑,3,   AQPs↓,1,   Bak↑,1,   BAX↑,1,   Bax:Bcl2↑,2,   Bcl-2↓,2,   Bcl-xL↓,1,   BIM↑,1,   BioAv↑,2,   cardioP↑,1,   CardioT↓,1,   Casp12?,1,   Casp3↑,4,   Casp8∅,1,   Casp9↑,3,   CD44↓,2,   CDK4↓,1,   chemoP↑,2,   ChemoSen↑,2,   ChemoSideEff↓,1,   cMYB↓,1,   COX2↓,1,   CSCs↓,1,   cycD1↓,1,   CYP1A1↓,1,   Cyt‑c↑,1,   DNMTs↓,1,   DR4↑,1,   DR5↑,2,   E-cadherin↑,1,   eff↓,5,   eff↑,7,   EGFR↓,1,   ER Stress↑,1,   ERK↓,2,   ERK↑,1,   ERK∅,1,   FOXO3↑,1,   Glycolysis↓,1,   GutMicro↝,1,   HDAC↓,5,   HER2/EBBR2↓,1,   Hif1a↓,5,   hTERT↓,1,   IAP1↓,1,   IFN-γ↑,1,   IL1β↓,1,   IL2↑,1,   IL6↓,1,   Inflam↓,1,   Mcl-1↓,1,   MEK↓,1,   miR-30a-5p↑,1,   MMP↓,2,   MMP1↓,1,   MMP2↓,4,   MMP9↓,3,   p‑mTOR↓,1,   neuroP↑,3,   NF-kB↓,3,   NOX↓,1,   NOXA↑,1,   NRF2↑,3,   p19↑,1,   P21↑,1,   p70S6↓,1,   cl‑PARP↑,2,   PI3K↓,1,   Prx↓,1,   RadioS↑,2,   p‑RB1↓,1,   ROS?,1,   ROS↓,1,   ROS↑,2,   selectivity↑,1,   Telomerase↓,1,   TNF-α↓,1,   TRAIL↑,1,   TumCCA?,1,   TumCCA↓,1,   TumCCA↑,1,   TumCD↑,1,   TumCG↓,2,   TumCP↓,1,   tumCV↓,1,   TumMeta↓,2,   TumW↓,2,   VEGF↓,5,   Wnt↓,2,   β-catenin/ZEB1↓,2,  
Total Targets: 94

Results for Effect on Normal Cells:
BioAv?,1,   BioAv↑,2,   Half-Life∅,2,   ROS↓,1,   toxicity↓,1,   toxicity∅,1,  
Total Targets: 6

Scientific Paper Hit Count for: angioG, angiogenesis
9 Sulforaphane (mainly Broccoli)
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:156  Target#:447  State#:%  Dir#:%
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