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


chemoP, ChemoProtective: Click to Expand ⟱
Source:
Type:
Protects normal cells against the effect of Chemo.
Scientific Papers found: Click to Expand⟱
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.

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).

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

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

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


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Results for Effect on Cancer/Diseased Cells:
angioG↓,2,   AntiCan↑,1,   antiOx↓,1,   Apoptosis↑,1,   AQPs↓,1,   BioAv↑,1,   cardioP↑,1,   Catalase↑,1,   chemoP↑,6,   ChemoSen↑,1,   CYP1A1↓,1,   Dose↝,1,   eff↑,1,   HDAC↓,3,   Hif1a↓,1,   HO-1↑,1,   Inflam↓,2,   Mets↑,1,   NAD↑,1,   neuroP↑,1,   NF-kB↓,2,   NOX↓,1,   Prx↓,1,   ROS↓,1,   ROS↑,1,   ROS⇅,2,   selectivity↑,1,   TumCCA↑,1,   TumCG↓,1,   tumCV↓,1,   TumMeta↓,1,  
Total Targets: 31

Results for Effect on Normal Cells:
Dose↝,1,   GSH↑,1,   GSTA1↑,1,   HO-1↑,1,   Inflam↓,1,   NQO1↑,2,   NRF2↑,3,   ROS↓,1,  
Total Targets: 8

Scientific Paper Hit Count for: chemoP, ChemoProtective
6 Sulforaphane (mainly Broccoli)
1 Chemotherapy
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:156  Target#:1171  State#:%  Dir#:%
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