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


CSCs, Cancer Stem Cells: Click to Expand ⟱
Source:
Type:
Cancer Stem Cells
Scientific Papers found: Click to Expand⟱
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↓,

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↓,

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↓,


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

Results for Effect on Cancer/Diseased Cells:
AIF↑,1,   ALDH↓,1,   ALDH1A1↓,2,   angioG↓,1,   Apoptosis↑,2,   BAX↑,1,   Bcl-2↓,1,   BioAv↓,1,   BioAv↑,1,   BMI1↓,1,   Casp↑,1,   Casp3↑,3,   Casp7↑,1,   Casp8↑,1,   Casp9↑,1,   CD133↓,2,   CD44↓,1,   CDK1↑,1,   ChemoSen↑,2,   ChemoSideEff↓,1,   COX2↓,1,   CSCs↓,9,   CXCR4↓,1,   cycD1↑,2,   Cyt‑c↑,1,   Diff↓,1,   DNAdam↑,1,   DNMT1↓,1,   DNMT3A↓,1,   E-cadherin↓,1,   eff↑,2,   EMT↓,2,   Gli↓,1,   Gli1↓,3,   GLI2↓,2,   GSTA1↑,1,   HDAC↓,1,   Hif1a↓,1,   hTERT↓,1,   IL1β↓,1,   MMP2↓,2,   MMP9↓,1,   Nanog↓,5,   Nestin↓,1,   NF-kB↓,3,   NOTCH↓,1,   NOTCH1↓,1,   NRF2↑,1,   OCT4↓,2,   P21↑,1,   p27↑,1,   P450↓,1,   PDGFRA↓,1,   PI3K↓,1,   ROS↑,1,   selectivity↑,1,   Shh↓,3,   Smo↓,3,   Snail↓,2,   SOX2↓,1,   TNF-α↓,1,   TumCCA↑,1,   TumCD↑,1,   TumCI↓,1,   TumCMig↓,2,   TumCP↓,1,   VEGF↓,1,   VEGFR2↓,1,   Wnt↓,3,   Zeb1↓,1,   β-catenin/ZEB1↓,2,  
Total Targets: 71

Results for Effect on Normal Cells:
BioAv↑,2,   Half-Life∅,1,   HDAC↓,1,   HDAC3↓,1,   Ki-67↓,1,  
Total Targets: 5

Scientific Paper Hit Count for: CSCs, Cancer Stem Cells
9 Sulforaphane (mainly Broccoli)
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:156  Target#:795  State#:%  Dir#:%
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