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 |
|