Sulforaphane (mainly Broccoli) / Hif1a Cancer Research Results

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

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 NRF2 / KEAP1 antioxidant response ↑ NRF2 (often insufficient for rescue) ↑ NRF2 (protective) Driver Electrophile-driven stress response Sulforaphane covalently modifies KEAP1, activating NRF2 signaling
2 Histone deacetylases (HDACs) ↓ HDAC activity ↔ mild modulation Driver Epigenetic reprogramming HDAC inhibition alters transcription of cell-cycle and apoptosis genes
3 Reactive oxygen species (ROS) ↑ ROS (transient / stress-inducing) ↓ ROS Secondary Redox signaling perturbation ROS rise reflects electrophilic stress rather than classic redox cycling
4 Cell cycle regulation ↑ G2/M or G1 arrest ↔ largely spared Secondary Cytostatic growth control Cell-cycle arrest is a prominent phenotype in cancer cells
5 Intrinsic apoptosis ↑ apoptosis (context-dependent) ↔ protected Phenotypic Threshold-dependent cell death Apoptosis occurs when stress exceeds adaptive capacity
6 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of inflammatory survival programs NF-κB inhibition supports anti-proliferative and anti-inflammatory effects


Hif1a, HIF1α/HIF1a: Click to Expand ⟱
Source:
Type:
Hypoxia-Inducible-Factor 1A (HIF1A gene, HIF1α, HIF-1α protein product)
-Dominantly expressed under hypoxia(low oxygen levels) in solid tumor cells
-HIF1A induces the expression of vascular endothelial growth factor (VEGF)
-High HIF-1α expression is associated with Poor prognosis
-Low HIF-1α expression is associated with Better prognosis

-Functionally, HIF-1α is reported to regulate glycolysis, whilst HIF-2α regulates genes associated with lipoprotein metabolism.
-Cancer cells produce HIF in response to hypoxia in order to generate more VEGF that promote angiogenesis

Key mediators of aerobic glycolysis regulated by HIF-1α.
-GLUT-1 → regulation of the flux of glucose into cells.
-HK2 → catalysis of the first step of glucose metabolism.
-PKM2 → regulation of rate-limiting step of glycolysis.
-Phosphorylation of PDH complex by PDK → blockage of OXPHOS and promotion of aerobic glycolysis.
-LDH (LDHA): Rapid ATP production, conversion of pyruvate to lactate;

HIF-1α Inhibitors:
-Curcumin: disruption of signaling pathways that stabilize HIF-1α (ie downregulate).
-Resveratrol: downregulate HIF-1α protein accumulation under hypoxic conditions.
-EGCG: modulation of upstream signaling pathways, leading to decreased HIF-1α activity.
-Emodin: reduce HIF-1α expression. (under hypoxia).
-Apigenin: inhibit HIF-1α accumulation.
Scientific Papers found: Click to Expand⟱
2448- SFN,    Sulforaphane and bladder cancer: a potential novel antitumor compound
- Review, Bladder, NA
Apoptosis↑, TumCG↓, TumCI↓, TumMeta↓, glucoNG↓, ChemoSen↑, TumCCA↑, Casp3↑, Casp7↑, cl‑PARP↑, survivin↓, EGFR↓, HER2/EBBR2↓, ATP↓, Glycolysis↓, mt-OXPHOS↓, AKT1↓, HK2↓, Hif1a↓, ROS↑, NRF2↑, EMT↓, COX2↓, MMP2↓, MMP9↓, Zeb1↓, Snail↓, HDAC↓, HATs↓, MMP↓, Cyt‑c↓, Shh↓, Smo↓, Gli1↓, BioAv↝, BioAv↝, Dose↝,
2556- SFN,    The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review
- Review, Var, NA
chemoPv↑, HDAC↓, Hif1a↓, angioG↓, CYP1A1↓, eff↑, BioAv↑,
2446- SFN,  CAP,    The Molecular Effects of Sulforaphane and Capsaicin on Metabolism upon Androgen and Tip60 Activation of Androgen Receptor
- in-vitro, Pca, LNCaP
AR↓, Bcl-xL↓, TumCP↓, Glycolysis↓, HK2↓, PKA↓, Hif1a↓, PSA↓, ECAR↓, BioAv↑, BioAv↓, *toxicity↓,
2406- SFN,    Sulforaphane and Its Protective Role in Prostate Cancer: A Mechanistic Approach
- Review, Pca, NA
HK2↓, PKM2↓, LDHA↓, Glycolysis↓, LAMP2↑, Hif1a↓, DNAdam↓, DNArepair↓, Dose↝,
1734- SFN,    Sulforaphane Inhibits Nonmuscle Invasive Bladder Cancer Cells Proliferation through Suppression of HIF-1α-Mediated Glycolysis in Hypoxia
- in-vitro, Bladder, RT112
selectivity↑, TumCP↓, Glycolysis↓, Hif1a↓,
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∅, ERK∅,
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↑, tumCV↓, TumCP↓, TumCCA↑, Apoptosis↑, cl‑Casp3↑, TumCI↓, VEGF↓, VEGFR2↓, Hif1a↓, eNOS↓, EMT?, TumCG↓, Ki-67↓, TUNEL↑, P21↑, p‑Chk2↑, CDC25↓, BAX↑, *ROS↓, NQO1?,
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↓, p38↓, ERK↓, AP-1↓, ROS↓, NF-kB↓, TumCI↓, MMP9↓, HDAC↓, Glycolysis↓, Hif1a↓, *memory↑, *cognitive↑,
1508- SFN,    Nrf2 targeting by sulforaphane: A potential therapy for cancer treatment
- Review, Var, NA
*BioAv↑, HDAC↓, TumCCA↓, eff↓, Wnt↓, β-catenin/ZEB1↓, Casp12?, Bcl-2↓, cl‑PARP↑, Bax:Bcl2↑, IAP1↓, Casp3↑, Casp9↑, Telomerase↓, hTERT/TERT↓, ROS?, DNMTs↓, angioG↓, VEGF↓, Hif1a↓, cMYB↓, MMP1↓, MMP2↓, MMP9↓, ERK↑, E-cadherin↑, CD44↓, MMP2↓, eff↑, IL2↑, IFN-γ↑, IL1β↓, IL6↓, TNF-α↓, NF-kB↓, ERK↓, NRF2↑, RadioS↑, ChemoSideEff↓,
1509- SFN,    Combination therapy in combating cancer
- Review, NA, NA
NRF2↑, ChemoSideEff↓, eff↑, TumCP↓, Apoptosis↑, TumCCA↑, eff↑, PSA↓, P53↑, Hif1a↓, CAIX↓, chemoR↓, 5HT↓,
1725- SFN,    Anticancer Activity of Sulforaphane: The Epigenetic Mechanisms and the Nrf2 Signaling Pathway
- Review, Var, NA
*toxicity∅, AntiCan↑, antiOx↑, NRF2↑, DNMTs↓, HDAC↓, Hif1a↓, VEGF↓, P21↑, TumCCA↑, ac‑H3↑, ac‑H4↑, DNAdam↑, Dose↝,
1726- SFN,    Sulforaphane: A Broccoli Bioactive Phytocompound with Cancer Preventive Potential
- Review, Var, NA
Dose↝, eff↝, IL1β↓, IL6↓, IL12↓, TNF-α↓, COX2↓, CXCR4↓, MPO↓, HSP70/HSPA5↓, HSP90↓, VCAM-1↓, IKKα↓, NF-kB↓, HO-1↑, Casp3↑, Casp7↑, Casp8↑, Casp9↑, cl‑PARP↑, Cyt‑c↑, Diablo↑, CHOP↑, survivin↓, XIAP↓, p38↑, Fas↑, PUMA↑, VEGF↓, Hif1a↓, Twist↓, Zeb1↓, Vim↓, MMP2↓, MMP9↓, E-cadherin↑, N-cadherin↓, Snail↓, CD44↓, cycD1/CCND1↓, cycA1/CCNA1↓, CycB/CCNB1↓, cycE/CCNE↓, CDK4↓, CDK6↓, p50↓, P53↑, P21↑, GSH↑, SOD↑, GSTs↑, mTOR↓, Akt↓, PI3K↓, β-catenin/ZEB1↓, IGF-1↓, cMyc↓, CSCs↓,
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↑, CSCs↓, Wnt↓, β-catenin/ZEB1↓, *BioAv↑, angioG↓, VEGF↓, Hif1a↓, MMP2↓, MMP9↓, Casp3↑, *Half-Life∅,
1484- SFN,    Sulforaphane’s Multifaceted Potential: From Neuroprotection to Anticancer Action
- Review, Var, NA - Review, AD, NA
neuroP↑, AntiCan↑, NRF2↑, HDAC↓, eff↑, *ROS↓, neuroP↑, HDAC↓, *toxicity∅, BioAv↑, eff↓, cycD1/CCND1↓, CDK4↓, p‑RB1↓, Glycolysis↓, miR-30a-5p↑, TumCCA↑, TumCG↓, TumMeta↓, eff↑, ChemoSen↑, RadioS↑, CardioT↓, angioG↓, Hif1a↓, VEGF↓, *BioAv?, *Half-Life∅,

Showing Research Papers: 1 to 14 of 14

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 14

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   CYP1A1↓, 1,   GSH↑, 1,   GSTs↑, 1,   HO-1↑, 1,   MPO↓, 1,   NQO1?, 1,   NRF2↑, 5,   mt-OXPHOS↓, 1,   ROS?, 1,   ROS↓, 1,   ROS↑, 1,   SOD↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   CDC25↓, 1,   MMP↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AKT1↓, 1,   CAIX↓, 1,   cMyc↓, 1,   ECAR↓, 1,   glucoNG↓, 1,   Glycolysis↓, 6,   HK2↓, 3,   LDHA↓, 1,   PKM2↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Akt∅, 1,   Apoptosis↑, 3,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp12?, 1,   Casp3↑, 4,   cl‑Casp3↑, 1,   Casp7↑, 2,   Casp8↑, 1,   Casp9↑, 2,   p‑Chk2↑, 1,   Cyt‑c↓, 1,   Cyt‑c↑, 1,   Diablo↑, 1,   Fas↑, 1,   hTERT/TERT↓, 1,   IAP1↓, 1,   p38↓, 1,   p38↑, 1,   PUMA↑, 1,   survivin↓, 2,   Telomerase↓, 1,   TumCD↑, 1,   TUNEL↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

ac‑H3↑, 2,   ac‑H4↑, 1,   HATs↓, 1,   miR-30a-5p↑, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   HSP70/HSPA5↓, 1,   HSP90↓, 1,  

Autophagy & Lysosomes ⓘ

LAMP2↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,   DNAdam↑, 1,   DNArepair↓, 1,   DNMTs↓, 2,   P53↑, 2,   cl‑PARP↑, 3,  

Cell Cycle & Senescence ⓘ

CDK4↓, 2,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 1,   P21↑, 3,   p‑RB1↓, 1,   TumCCA↓, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State ⓘ

CD44↓, 2,   cMYB↓, 1,   CSCs↓, 2,   EMT?, 1,   EMT↓, 1,   ERK↓, 2,   ERK↑, 1,   ERK∅, 1,   Gli1↓, 1,   HDAC↓, 8,   IGF-1↓, 1,   mTOR↓, 1,   PI3K↓, 1,   Shh↓, 1,   Smo↓, 1,   TumCG↓, 3,   Wnt↓, 2,  

Migration ⓘ

AP-1↓, 1,   E-cadherin↑, 2,   Ki-67↓, 1,   MMP1↓, 1,   MMP2↓, 5,   MMP9↓, 6,   N-cadherin↓, 1,   PKA↓, 1,   Snail↓, 2,   TumCI↓, 3,   TumCP↓, 4,   TumMeta↓, 2,   Twist↓, 1,   VCAM-1↓, 1,   Vim↓, 1,   Zeb1↓, 2,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature ⓘ

angioG↓, 5,   EGFR↓, 1,   eNOS↓, 1,   Hif1a↓, 14,   VEGF↓, 7,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CXCR4↓, 1,   IFN-γ↑, 1,   IKKα↓, 1,   IL12↓, 1,   IL1β↓, 2,   IL2↑, 1,   IL6↓, 2,   NF-kB↓, 3,   p50↓, 1,   PSA↓, 2,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

5HT↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 3,   BioAv↝, 2,   chemoR↓, 1,   ChemoSen↑, 3,   Dose↝, 4,   eff↓, 2,   eff↑, 6,   eff↝, 1,   RadioS↑, 2,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   HER2/EBBR2↓, 1,   hTERT/TERT↓, 1,   IL6↓, 2,   Ki-67↓, 1,   PSA↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 2,   CardioT↓, 1,   chemoPv↑, 1,   ChemoSideEff↓, 2,   neuroP↑, 2,  
Total Targets: 156

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv?, 1,   BioAv↑, 2,   Half-Life∅, 2,  

Functional Outcomes ⓘ

cognitive↑, 1,   memory↑, 1,   toxicity↓, 1,   toxicity∅, 2,  
Total Targets: 8

Scientific Paper Hit Count for: Hif1a, HIF1α/HIF1a
14 Sulforaphane (mainly Broccoli)
1 Capsaicin
1 Gemcitabine (Gemzar)
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:156  Target#:143  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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