Quercetin / chemoP Cancer Research Results

QC, Quercetin: Click to Expand ⟱
Features:
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


chemoP, ChemoProtective: Click to Expand ⟱
Source:
Type:
Protects normal cells against the effect of Chemo.
Scientific Papers found: Click to Expand⟱
26- EGCG,  QC,  docx,    Green tea and quercetin sensitize PC-3 xenograft prostate tumors to docetaxel chemotherapy
- vitro+vivo, Pca, PC3
BAD↓,
cl‑PARP↑,
Casp7↑,
IκB↓,
Ki-67↓,
VEGF↓,
EGFR↓,
FGF↓,
TGF-β↓,
TNF-α↓,
SCF↓,
Bax:Bcl2↑,
NF-kB↓,
chemoP↑, This study provides a novel regimen to enhance the therapeutic effect of Doc in a less-toxic manner and reduce its risk of side effects in treatment of CRPC.
ChemoSen↑, GT and Q with LD Doc significantly enhanced the potency of Doc 2-fold and reduced tumor growth by 62 % compared to LD Doc in 7-weeks intervention.
TumVol↓,

2303- QC,  doxoR,    Quercetin greatly improved therapeutic index of doxorubicin against 4T1 breast cancer by its opposing effects on HIF-1α in tumor and normal cells
- in-vitro, BC, 4T1 - in-vivo, NA, NA
cardioP↑, Quercetin had better cardioprotective and hepatoprotective activities.
hepatoP↑,
TumCG↓, In vivo, quercetin suppressed tumor growth and prolonged survival in BALB/c mice bearing 4T1 breast cancer.
OS↑,
ChemoSen↑, quercetin enhanced therapeutic efficacy of DOX and simultaneously reduced DOX-induced toxic side effects
chemoP↑, IC50 of DOX in combination with quercetin 10 or 25 uM was increased by three- and fourfold, respectively, compared with that of DOX alone
Hif1a↓, Further study showed that quercetin suppressed intratumoral HIF-1α in a hypoxia-dependent way but increased its accumulation in normal cells
*Hif1a↑,
selectivity↑, quercetin could improve therapeutic index of DOX by its opposing effects on HIF-1α in tumor and normal cells
TumVol↓,
OS↑,

68- QC,  BaP,    Differential protein expression of peroxiredoxin I and II by benzo(a)pyrene and quercetin treatment in 22Rv1 and PrEC prostate cell lines
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, PrEC
PrxI∅, Prx-I, Prx-II PrEC cells
PrxII∅, PrEC cells
*toxicity↓, lack of quercetin-mediated changes in Prx expression suggests that quercetin does not interfere with H2O2 levels, and thus may have no deleterious effect in normal prostate cells
ROS↓, <10uM Quercetin
ROS↑, BaP-mediated toxicity in both 22Rv1 and PrEC cells was confirmed by a significant increase in reactive oxygen species
ROS∅, Quercetin also antagonized the increase in ROS by BaP which suggests that BaP-mediated oxidative stress could be blocked with quercetin in 22Rv1 and PrEC cells. S
chemoP↑, Studies have shown that quercetin can be a potential chemopreventative agent in prostate cancer.
PrxII↑, A physiologically achievable concentration (5uM) of quercetin increased the expression of Prx II without affecting the Prx I levels in 22Rv1 cells
i-H2O2↓, Upregulation of Prx II may reduce the intracellular levels of H 2 O2 which in turn can interfere with growth signaling pathways suppressing cell proliferation.

4787- QC,    Quercetin: A Phytochemical with Pro-Apoptotic Effects in Colon Cancer Cells
- Review, CRC, NA
Inflam↓, quercetin, has been shown to have anti-inflammatory and anti-carcinogenic effects
AntiCan↑,
Apoptosis↑, nduce apoptosis via the mitochondrial apoptotic pathway by causing changes in the mitochondrial membrane potential.
MMP↓,
P53↑, quercetin also induces apoptosis through the activation of p53, increasing the expression of pro-apoptotic molecules such as Bax, caspase-3, caspase-9, and inhibition of anti-apoptotic proteins such as Bcl-2
BAX↑,
Casp3↑,
Casp9↑,
Bcl-2↓,
NF-kB↓, Quercetin might exert anti-inflammatory properties by suppressing NF-kB translocation and the expression of pro-inflammatory cytokines such as tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), IL-1b
IL6↓,
IL1β↓,
*antiOx↑, Quercetin is a powerful antioxidant and lipid peroxidation inhibitor, thanks to its catechol and hydroxyl group configuration, its capacity to scavenge free radicals and to bind metal ions.
*lipid-P↓,
*ROS↓,
MAPK↓, Quercetin has the potential to exert an anti-cancer effect by inhibiting important signaling pathways in carcinogenesis such as MAPK, JAK-STAT, and PI3K-Akt.
JAK↓,
STAT↓,
PI3K↓,
Akt↓,
chemoP↑, Quercetin is a lipophilic compound which can cross the cell membrane and activate multiple intracellular signaling pathways in chemoprevention
ROS⇅, dual function as a pro-oxidant or anti-oxidant. Oxidative stress caused by ROS species causes DNA damage and mutation development.
DNAdam↑,
ChemoSen↝, Therefore, it is thought that quercetin can be applied as a supplement in cancer treatment in combination with existing chemotherapies.


Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

i-H2O2↓, 1,   PrxI∅, 1,   PrxII↑, 1,   PrxII∅, 1,   ROS↓, 1,   ROS↑, 1,   ROS⇅, 1,   ROS∅, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↑, 1,   BAD↓, 1,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   Casp7↑, 1,   Casp9↑, 1,   MAPK↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   P53↑, 1,   cl‑PARP↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

FGF↓, 1,   PI3K↓, 1,   SCF↓, 1,   STAT↓, 1,   TumCG↓, 1,  

Migration(tgid=13) ⓘ

Ki-67↓, 1,   TGF-β↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IL1β↓, 1,   IL6↓, 1,   Inflam↓, 1,   IκB↓, 1,   JAK↓, 1,   NF-kB↓, 2,   TNF-α↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 2,   ChemoSen↝, 1,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 1,   IL6↓, 1,   Ki-67↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   cardioP↑, 1,   chemoP↑, 4,   hepatoP↑, 1,   OS↑, 2,   TumVol↓, 2,  
Total Targets: 51

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   lipid-P↓, 1,   ROS↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↑, 1,  

Functional Outcomes(tgid=23) ⓘ

toxicity↓, 1,  
Total Targets: 5

Scientific Paper Hit Count for: chemoP, ChemoProtective
4 Quercetin
1 EGCG (Epigallocatechin Gallate)
1 Docetaxel
1 doxorubicin
1 benzo(a)pyrene
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#:140  Target#:1171  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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