Plant pigment (flavonoid) found in red wine, onions, green tea, apples and berries.
Quercetin is thought to contribute to anticancer effects through several mechanisms:
-Antioxidant Activity:
-Induction of Apoptosis:modify Bax:Bcl-2 ratio
-Anti-inflammatory Effects:
-Cell Cycle Arrest:
-Inhibition of Angiogenesis and Metastasis: (VEGF)
Cellular Pathways:
-PI3K/Akt/mTOR Pathway: central to cell proliferation, survival, and metabolism.
-MAPK/ERK Pathway: influencing cell proliferation, differentiation, and apoptosis.
-NF-κB Pathway: downregulate NF-κB
-JAK/STAT Pathway: interfere with the activation of STAT3
-Apoptotic Pathways: intrinsic (mitochondrial) and extrinsic (death receptor-mediated) pathways
Quercetin has been used at doses around 500–1000 mg per day
Quercetin’s bioavailability from foods or standard supplements can be low.
EMIQ bioavialability is about 3X that of Quercetin (Example Natural Factors brand)
Isoquercitrin is high bioaviability and efficiacy but at this time does not seem available as supplement.
-Note half-life 11 to 28 hours.
BioAv low 1-10%, poor water-solubility, consuming with fat may improve bioavialability. also piperine or VitC.
Pathways:
- induce
ROS production in cancer cells (higher dose). Typicallys Lowers ROS in normal cells(unless it is high dose?)or depends on Redox status?. "quercetin paradox"
- ROS↑ related:
MMP↓(ΔΨm),
ER Stress↑,
UPR↑,
GRP78↑,
Ca+2↑,
Cyt‑c↑,
Caspases↑,
DNA damage↑,
cl-PARP↑,
HSP↓,
Prx,
- Confusing info about Lowering AntiOxidant defense in Cancer Cells:
NRF2↓(some contrary),
TrxR↓**,
SOD↓(contrary),
GSH↓
Catalase↓(contrary),
HO1↓(some contrary),
GPx↓(some contrary)
- 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↓,
TIMP2,
IGF-1↓,
uPA↓,
VEGF↓,
ROCK1↓,
FAK↓,
NF-κB↓,
CXCR4↓,
SDF1↓,
TGF-β↓,
α-SMA↓,
ERK↓
- reactivate genes thereby inhibiting cancer cell growth :
HDAC↓,
DNMTs↓,
EZH2↓,
P53↑,
HSP↓,
Sp proteins↓,
TET↑
- cause Cell cycle arrest :
TumCCA↑,
cyclin D1↓,
cyclin E↓,
CDK2↓,
CDK4↓,
CDK6↓,
- inhibits Migration/Invasion :
TumCMig↓,
TumCI↓,
TNF-α↓,
FAK↓,
ERK↓,
EMT↓,
TOP1↓,
TET1,
- inhibits
glycolysis
and
ATP depletion :
HIF-1α↓,
PKM2↓,
cMyc↓,
GLUT1↓,
LDH↓,
LDHA↓,
HK2↓,
PFKs↓,
PDKs↓,
ECAR↓,
OXPHOS↓,
GRP78↑,
GlucoseCon↓
- inhibits
angiogenesis↓ :
VEGF↓,
HIF-1α↓,
Notch↓,
FGF↓,
PDGF↓,
EGFR↓,
- some indication of inhibiting Cancer Stem Cells :
CSC↓,
CK2↓,
Hh↓,
CD24↓,
β-catenin↓,
Notch2↓,
- Others: PI3K↓,
AKT↓,
JAK↓,
STAT↓,
Wnt↓,
β-catenin↓,
AMPK,
α↓,
ERK↓,
JNK,
- 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 |
Reactive oxygen species (ROS) |
↑ ROS (dose-, metal-, context-dependent) |
↓ ROS |
Conditional Driver |
Biphasic redox modulation |
Quercetin exhibits pro-oxidant behavior in cancer cells while protecting normal cells |
| 2 |
Mitochondrial integrity / intrinsic apoptosis |
↓ ΔΨm; ↑ caspase activation |
↔ preserved |
Driver |
Execution of intrinsic apoptosis |
Mitochondrial dysfunction is a central apoptosis route in cancer cells |
| 3 |
PI3K → AKT → mTOR axis |
↓ AKT / ↓ mTOR |
↔ adaptive suppression |
Driver |
Growth and survival inhibition |
AKT/mTOR suppression is a consistently reported upstream effect in cancer models |
| 4 |
NF-κB signaling |
↓ NF-κB activation |
↓ inflammatory NF-κB tone |
Secondary |
Reduced survival and inflammatory transcription |
NF-κB inhibition contributes to chemosensitization and apoptosis susceptibility |
| 5 |
MAPK signaling (JNK / p38) |
↑ JNK / ↑ p38 |
↔ minimal |
Secondary |
Stress-mediated apoptosis signaling |
MAPK activation supports apoptosis downstream of redox stress |
| 6 |
Cell cycle regulation |
↑ G1/S or G2/M arrest |
↔ largely spared |
Phenotypic |
Cytostatic growth control |
Cell-cycle arrest reflects disruption of growth signaling |
| 7 |
HIF-1α hypoxia signaling |
↓ HIF-1α |
↔ minimal |
Secondary |
Reduced hypoxia tolerance |
Quercetin interferes with hypoxia-driven transcriptional programs |
| 8 |
NRF2 antioxidant response |
↑ NRF2 (adaptive, context-dependent) |
↑ NRF2 (protective) |
Adaptive |
Stress compensation |
NRF2 induction reflects redox buffering rather than primary cytotoxicity |
|