Database Query Results : Quercetin, , chemoP

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.

-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


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


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   AntiCan↑,1,   Apoptosis↑,1,   BAX↑,1,   Bcl-2↓,1,   cardioP↑,1,   Casp3↑,1,   Casp9↑,1,   chemoP↑,3,   ChemoSen↑,1,   ChemoSen↝,1,   DNAdam↑,1,   i-H2O2↓,1,   hepatoP↑,1,   Hif1a↓,1,   IL1β↓,1,   IL6↓,1,   Inflam↓,1,   JAK↓,1,   MAPK↓,1,   MMP↓,1,   NF-kB↓,1,   OS↑,2,   P53↑,1,   PI3K↓,1,   PrxI∅,1,   PrxII↑,1,   PrxII∅,1,   ROS↓,1,   ROS↑,1,   ROS⇅,1,   ROS∅,1,   selectivity↑,1,   STAT↓,1,   TumCG↓,1,   TumVol↓,1,  
Total Targets: 36

Results for Effect on Normal Cells:
antiOx↑,1,   Hif1a↑,1,   lipid-P↓,1,   ROS↓,1,   toxicity↓,1,  
Total Targets: 5

Scientific Paper Hit Count for: chemoP, ChemoProtective
3 Quercetin
1 doxorubicin
1 benzo(a)pyrene
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:140  Target#:1171  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page