Database Query Results : Quercetin, , TumCG

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

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


TumCG, Tumor cell growth: Click to Expand ⟱
Source:
Type:
Normal cells grow and divide in a regulated manner through the cell cycle, which consists of phases (G1, S, G2, and M).
Cancer cells often bypass these regulatory mechanisms, leading to uncontrolled proliferation. This can result from mutations in genes that control the cell cycle, such as oncogenes (which promote cell division) and tumor suppressor genes (which inhibit cell division).
Scientific Papers found: Click to Expand⟱
380- AgNPs,  QC,  CA,  Chit,    Quercetin- and caffeic acid-functionalized chitosan-capped colloidal silver nanoparticles: one-pot synthesis, characterization, and anticancer and antibacterial activities
- in-vitro, MG, U118MG
TumCG↓, cell viability has constantly decreased by increasing the concentration

911- QC,  SFN,    Pilot study evaluating broccoli sprouts in advanced pancreatic cancer (POUDER trial) - study protocol for a randomized controlled trial
TumCG↓,
Risk↓, decreased risk of extra-prostatic manifestation of prostate cancer: cruciferous vegetables, in particular broccoli which is rich in sulforaphane and quercetin

99- QC,    Quercetin Inhibits Epithelial-to-Mesenchymal Transition (EMT) Process and Promotes Apoptosis in Prostate Cancer via Downregulating lncRNA MALAT1
- in-vitro, Pca, PC3
EMT↓, quercetin suppressed EMT process, promote apoptosis and deactivated PI3K/Akt signaling pathway in PC-3 cells
E-cadherin↑, Quercetin increased E-cadherin expression and decreased the level of N-cadherin
N-cadherin↓,
Ki-67↓, while the production of Ki67 was significantly reduced by quercetin
PI3K/Akt↓,
MALAT1↓, MALAT1 expression was significantly downregulated in quercetin-treated PC cells at a dose- and time-dependent manne
TumCG↓, Quercetin Inhibited Tumor Growth by Targeting MALAT1 in vivo

2340- QC,    Oral Squamous Cell Carcinoma Cells with Acquired Resistance to Erlotinib Are Sensitive to Anti-Cancer Effect of Quercetin via Pyruvate Kinase M2 (PKM2)
- in-vitro, OS, NA
TumCG↓, At a concentration of 5 μM, quercetin effectively arrested cell growth, reduced glucose utilization, and inhibited cellular invasiveness
GlucoseCon↓,
TumCI↓,
GLUT1↓, Quercetin also prominently down-regulated GLUT1, PKM2, and lactate dehydrogenase A (LDHA) expression of erlotinib-resistant HSC-3 cells
PKM2↓,
LDHA↓,
Glycolysis↓, Moreover, quercetin (30 μM) suppressed glycolysis in the MCF-7 and MDA-MB-231 breast cancer cells, as evidenced by decreased glucose uptake and lactate production with a concomitant decrease in the levels of the GLUT1, PKM2, and LDHA proteins [29].
lactateProd↓,
HK2↓, Hexokinase 2 (HK2)-mediated glycolysis was also shown to be inhibited following quercetin treatment (25~50 μM) in Bel-7402 and SMMC-7721 hepatocellular carcinoma (HCC) cells
eff↑, Downregulation of PKM2 also potently restored sensitivity to the inhibitory effect of erlotinib on cell growth and invasion

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↑,

53- QC,    Quercetin regulates β-catenin signaling and reduces the migration of triple negative breast cancer
- in-vitro, BC, MDA-MB-231 - NA, NA, MDA-MB-468
E-cadherin↑, quercetin can induce the expression of E-cadherin and also downregulate vimentin levels in TNBC
Vim↓,
cycD1/CCND1↓,
cMyc↓,
EMT↓, tumor cells
TumCG↓, Quercetin Decreased the Growth and Cell Survival of TNBC Cells
TumCMig↓, Quercetin Induced Change in Cell Morphology and Inhibited Cell Migration of TNBC Cell
β-catenin/ZEB1↓, Quercetin Treatment Inactivated b-Catenin
ChemoSen↑, Quercetin decreased the TGF-b1 signaling (Figure 6C) and also enhanced the ability of doxorubicin to decrease the migratory potential of TNBC.

55- QC,    Quercetin inhibits the growth of human gastric cancer stem cells by inducing mitochondrial-dependent apoptosis through the inhibition of PI3K/Akt signaling
- in-vitro, GC, GCSCs
Bcl-2↓,
BAX↑,
Cyt‑c↑, upregulation of Cyt-c following treatment with quercetin
MMP↓, quercetin-induced apoptosis occurred via the mitochondrial-dependent pathway, which was mediated via the PI3K-Akt pathway.
PI3K/Akt↓,
Casp3↑,
Casp9↑,
TumCG↓, quercetin has the potential to effectively intervene and prevent GCSC growth
Apoptosis↑,
CSCs↓, Quercetin inhibits the growth of human gastric cancer stem cells

43- QC,    Investigation of the anti-cancer effect of quercetin on HepG2 cells in vivo
- in-vivo, Liver, HepG3
cycD1/CCND1↓, quercetin could significantly inhibit the growth and proliferation of HepG2 cells by regulating the gene expression of cyclin D1
TumCG↓,
TumCP↓,

50- QC,    Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer
- vitro+vivo, Ovarian, A2780S
Casp3↑, Quercetin treatment induced the apoptosis of A2780S cells associated with activating caspase-3 and caspase-9.
Casp9↑,
Mcl-1↓, MCL-1 downregulation, Bcl-2 downregulation, Bax upregulation and mitochondrial transmembrane potential change were observed
Bcl-2↓,
BAX↑,
angioG↓, inhibiting angiogenesis in vivo.
TumCG↓, QU inhibited the growth of A2780S ovarian cancer cells on a dose dependent manner in vitro
Apoptosis↑, quercetin may induce apoptosis of A2780S cells through the mitochondrial apoptotic pathway
p‑p44↓, quercetin treatment decreased phosphorylated p44/42 mitogen-activated protein kinase and phosphorylated Akt, contributing to inhibition of A2780S cell proliferation.
Akt↓,
TumCP↓,
eff↑, Our data suggested that QU/MPEG-PCL micelles were a novel nano-formulation of quercetin with a potential clinical application in ovarian cancer therapy.

97- QC,  HPT,    Effects of the flavonoid drug Quercetin on the response of human prostate tumours to hyperthermia in vitro and in vivo
- in-vitro, Pca, PC3
HSP72↑, Quercetin in prostate cancer treatment is that it antagonizes HSP72 production and, thus, sensi- tizes cells to hyperthermia-induce d apoptosis
TumCG↓, Quercetin dose-dependently suppressed PC-3 tumour growth in vitro and in vivo.
eff↑, suggest the use of Quercetin as a hyperthermia sensitizer in the treatment of prostate carcinoma
ChemoSen↑, Quercetin can act as a sensitizer to hyperthermia (® gures 1± 5), chemotherapeutic agents and ionizing radiation4,20
RadioS↑,

94- QC,  HPT,    Effects of quercetin on the heat-induced cytotoxicity of prostate cancer cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, PC3 - in-vitro, Pca, JCA-1
HSP70/HSPA5↓, Quercetin inhibited an increase of hsp70 expression after heat treatment and increased the number of subG1 cells with lower levels of hsp70 in JCA-1 and LNcap cells.
TumCCA↑,
TumCG↓, Quercetin inhibited the growth of JCA-1 and LNcap cells at concentrations over 12.5 mmol/L.
eff↑, the presence of quercetin during heating enhances the growth-inhibitory effect of heat by inducing apoptosis in the JCA-1 and LNcap cells.

88- QC,  PacT,    Quercetin Enhanced Paclitaxel Therapeutic Effects Towards PC-3 Prostate Cancer Through ER Stress Induction and ROS Production
- vitro+vivo, Pca, PC3
ROS↑, quercetin and paclitaxel significantly inhibited cell proliferation, increased apoptosis, arrested the cell cycle at the G2/M phase, inhibited cell migration, dramatically induced ER stress to occur, and increased ROS generation.
ER Stress↑,
TumCP↓,
Apoptosis↑,
TumCCA↑,
TumCMig↓,
GRP78/BiP↑, The combined group effectively decreased hnRNPA1 gene expressions and increased the GRP78 and CHOP gene expressions, which are related to ER stress and ROS production
CHOP↑,
TumCG↓, In vivo Tumor Growth Inhibition

73- QC,    The dietary bioflavonoid, quercetin, selectively induces apoptosis of prostate cancer cells by down-regulating the expression of heat shock protein 90
- in-vitro, Pca, LNCaP - in-vitro, Pca, DU145 - in-vitro, Pca, PC3
HSP90↓, quercetin down-regulates the expression of Hsp90 which, in turn, induces inhibition of growth and cell death in prostate cancer cells
Casp3↑, quercetin increased caspase-3 and caspase-9 activities in both LNCaP and PC-3 cells, whereas dihydroquercetin had no effect on caspases
Casp9↑,
TumCG↓,
TumCD↑,
selectivity↑, while exerting no quantifiable effect on normal prostate epithelial cells.
toxicity↓, quercetin at doses of 40–1,900 mg/kg/day in rats showed no signs of toxicity or death

77- QC,  EGCG,    The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition
- in-vitro, Pca, CD44+ - in-vitro, NA, CD133+ - in-vitro, NA, PC3 - in-vitro, NA, LNCaP
Casp3↑, EGCG induces apoptosis by activating capase-3/7 and inhibiting the expression of Bcl-2, survivin and XIAP in CSCs.
Casp7↑,
Bcl-2↓,
survivin↓,
XIAP↓,
EMT↓, EGCG inhibits epithelial-mesenchymal transition by inhibiting the expression of vimentin, slug, snail and nuclear β-catenin, and the activity of LEF-1/TCF
Vim↓,
Slug↓,
Snail↓,
β-catenin/ZEB1↓,
LEF1↓, LEF1/TCF
TCF↓, LEF1/TCF
eff↑, inhibition of Nanog by shRNA enhanced the inhibitory effects of EGCG
CSCs↓, prostate cancer cell lines contain a small population of CD44+CD133+ cancer stem cells and their self-renewal capacity is inhibited by EGCG.
TumCG↓, EGCG inhibits the growth of cancer stem cells isolated from human prostate cancer cell lines
tumCV↓, EGCG inhibits the formation of primary and secondary tumor spheroids and cell viability of human prostate cancer stem cells

3371- QC,    Quercetin induces MGMT+ glioblastoma cells apoptosis via dual inhibition of Wnt3a/β-Catenin and Akt/NF-κB signaling pathways
- in-vitro, GBM, T98G
TIMP2↑, MMP2, and MMP9 was significantly decreased by quercetin treatment, while TIMP1 and TIMP2 were upregulated (
TumCG↓, Quercetin significantly suppressed the growth and migration of human GBM T98G cells, induced apoptosis, and arrested cells in the S-phase cell cycle
TumCMig↓,
Apoptosis↑,
TumCCA↑,
MMP↓, collapse of mitochondrial membrane potential, ROS generation, enhanced Bax/Bcl-2 ratio, and strengthened cleaved-Caspase 9 and cleaved-Caspase 3 suggested the involvement of ROS-mediated mitochondria-dependent apoptosis in the process
ROS↑,
Bax:Bcl2↑,
cl‑Casp9↑,
cl‑Casp3↑,
DNAdam↑, quercetin-induced apoptosis was accompanied by intense DNA double-strand breaks (DSBs), γH2AX foci formation, methylation of MGMT promoter, increased cleaved-PARP, and reduced MGMT expression
γH2AX↑,
MGMT↓,
cl‑PARP↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↓, 1,   LDHA↓, 1,   PI3K/Akt↓, 2,   PKM2↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 4,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 3,   Casp3↑, 4,   cl‑Casp3↑, 1,   Casp7↑, 1,   Casp9↑, 3,   cl‑Casp9↑, 1,   Cyt‑c↑, 1,   Mcl-1↓, 1,   survivin↓, 1,   TumCD↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   HSP70/HSPA5↓, 1,   HSP72↑, 1,   HSP90↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   MGMT↓, 1,   cl‑PARP↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 2,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 2,   EMT↓, 3,   TCF↓, 1,   TumCG↓, 15,  

Migration ⓘ

E-cadherin↑, 2,   Ki-67↓, 1,   LEF1↓, 1,   MALAT1↓, 1,   N-cadherin↓, 1,   p‑p44↓, 1,   Slug↓, 1,   Snail↓, 1,   TIMP2↑, 1,   TumCI↓, 1,   TumCMig↓, 3,   TumCP↓, 3,   Vim↓, 2,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 3,   eff↑, 5,   RadioS↑, 1,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

Ki-67↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   chemoP↑, 1,   hepatoP↑, 1,   OS↑, 2,   Risk↓, 1,   toxicity↓, 1,   TumVol↓, 1,  
Total Targets: 71

Pathway results for Effect on Normal Cells:


Angiogenesis & Vasculature ⓘ

Hif1a↑, 1,  
Total Targets: 1

Scientific Paper Hit Count for: TumCG, Tumor cell growth
15 Quercetin
2 Hyperthermia
1 Silver-NanoParticles
1 Caffeic acid
1 chitosan
1 Sulforaphane (mainly Broccoli)
1 doxorubicin
1 Paclitaxel
1 EGCG (Epigallocatechin Gallate)
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#:323  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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