Quercetin / Akt 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

Akt, PKB-Protein kinase B: Click to Expand ⟱

Source: HalifaxProj(inhibit)

Type:

Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes; Akt2 is an important signaling molecule in the insulin signaling pathway. It is required to induce glucose transport.

Inhibitors:
-Curcumin: downregulate AKT phosphorylation and signaling.
-Resveratrol
-Quercetin: inhibit the PI3K/AKT pathway.
-Epigallocatechin Gallate (EGCG)
-Luteolin and Apigenin: inhibit AKT phosphorylation

Scientific Papers found: Click to Expand⟱

3338-

QC,

Quercetin: Its Antioxidant Mechanism, Antibacterial Properties and Potential Application in Prevention and Control of Toxipathy

Review,

Var,

Review,

Stroke,

*antiOx↑, The antioxidant mechanism of quercetin in vivo is mainly reflected in its effects on glutathione (GSH), signal transduction pathways, reactive oxygen species (ROS), and enzyme activities.
*GSH↑,
*ROS↓,
*Dose↑, antioxidant properties of quercetin show a concentration dependence in the low dose range but too much of the antioxidant brings about the opposite result
*NADPH↓, quercetin counteracts atherosclerosis by reversing the increased expression of NADPH oxidase i
*AMP↓, decreases in activation of AMP-activated protein kinase, thereby inhibiting NF-κB signaling
*NF-kB↓,
*p38↑, quercetin improves the antioxidant capacity of cells by activating the intracellular p38 MAPK pathway, increasing intracellular GSH levels and providing a source of hydrogen donors in the scavenging of free radical reactions.
*MAPK↑,
*SOD↑, quercetin achieves protection against acute spinal cord injury by up-regulating the activity of SOD, down-regulating the level of malondialdehyde (MDA), and inhibiting the p38MAPK/iNOS signaling pathway
*MDA↓,
*iNOS↓,
*Catalase↑, quercetin reduces imiquimod (IMQ)-induced MDA levels in skin tissues and enhances catalase, SOD, and GSH activities, which together improve the antioxidant properties of the body
*PI3K↑, It also controls the development of atherosclerosis induced by high fructose diet by enhancing PI3K/AKT and inhibiting ROS
*Akt↑,
*lipid-P↓, Quercetin enhances antioxidant activity and inhibits lipid cultivation, and it is effective in the treatment of oxidative liver damag
*memory↑, reversed hypoxia-induced memory impairment
*radioP↑, Quercetin protects cells from radiation and genotoxicity-induced damage by increasing endogenous antioxidant and scavenging free radical levels
*neuroP↑, This suggests that quercetin may be a potential neuroprotective agent against ischemia, which protects CA1 vertebral neurons from I/R injury in the hippocampal region of animals
*MDA↓, quercetin significantly reduced MDA levels and increased SOD and catalase levels.

2342-

QC,

Quercetin Inhibits the Proliferation of Glycolysis-Addicted HCC Cells by Reducing Hexokinase 2 and Akt-mTOR Pathway

in-vitro,

HCC,

Bel-7402

in-vitro,

HCC,

SMMC-7721 cell

in-vivo,

NA,

mouse

TumCP↓, In the present study, we reported that QUE inhibited the proliferation of HCC cells that relied on aerobic glycolysis.
HK2↓, QUE could decrease the protein levels of HK2 and suppress the AKT/mTOR pathway in HCC cells
Akt↓,
mTOR↓,
GlucoseCon↓, glucose uptake and lactate production of SMMC-7721 and Bel-7402 decreased in a dose-dependent manner after QUE treatment
lactateProd↓,
Glycolysis↓, QUE can inhibit the glycolysis of cancer cells, thereby inhibiting the progression of multiple cancers

2341-

QC,

Quercetin suppresses the mobility of breast cancer by suppressing glycolysis through Akt-mTOR pathway mediated autophagy induction

in-vitro,

BC,

MCF7

30Î¼M

in-vitro,

BC,

MDA-MB-231

in-vivo,

NA,

intraperitoneally injected with 50 mg/kg quercetin twice daily for a
month

mice

MMP2↓, quercetin treatment down-regulated the expression of cell migration marker proteins, such as matrix metalloproteinase 2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF).
MMP9↓, level of MMP-2, MMP-9 and VEGF was all strongly cut down by quercetin treatment compared with control group
VEGF↓,
Glycolysis↓, quercetin successfully blocked cell glycolysis by inhibiting the level of glucose uptake and the production of lactic acid
lactateProd↓,
PKM2↓, and also decreased the level of glycolysis-related proteins Pyruvate kinase M2 (PKM2), Glucose transporter1(GLUT1) and Lactate dehydrogenase A (LDHA).
GLUT1↓,
LDHA↓,
TumAuto↑, quercetin induced obvious autophagy via inactivating the Akt-mTOR pathway
Akt↓,
mTOR↓,
TumMeta↓, Quercetin suppressed the progression of breast cancer by inhibiting tumor metastasis and glycolysis in vivo
MMP3↓, quercetin effectively suppressed the invasion and migration ability of breast cancer cells through suppressing the expression of MMP-3, MMP-9 and VEGF,
eff↓, down-regulating the expression of PKM2, which regulated the final step of glycolysis, could effectively enhance the chemotherapeutic effect of THP
GlucoseCon↓, we found that quercetin effectively suppressed the level of glucose uptake and the production of lactic acid, and also down-regulated the expression of glycolysis-related proteins PKM2, LDHA and GLUT1,
lactateProd↓,
TumAuto↑, quercetin treatment induced obvious autophagy in MCF-7 and MDA-MB-231 cells via inactivating the Akt-mTOR pathway
LC3B-II↑, showing obvious conversion of LC3B-I to LC3B-II

923-

QC,

Quercetin as an innovative therapeutic tool for cancer chemoprevention: Molecular mechanisms and implications in human health

Review,

Var,

ROS↑, decided by the availability of intracellular reduced glutathione (GSH),
GSH↓, extended exposure with high concentration of quercetin causes a substantial decline in GSH levels
Ca+2↝,
MMP↓,
Casp3↑, activation of caspase-3, -8, and -9
Casp8↑,
Casp9↑,
other↓, when p53 is inhibited, cancer cells become vulnerable to quercetin-induced apoptosis
*ROS↓, Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors.
*NRF2↑, Moreover, the therapeutic efficacy of QC has also been defined in rat models through the activation of Nrf-2/HO-1 against high glucose-induced damage
HO-1↑,
TumCCA↑, QC increases cell cycle arrest via regulating p21WAF1, cyclin B, and p27KIP1
Inflam↓, QC-mediated anti-inflammatory and anti-apoptotic properties play a key role in cancer prevention by modulating the TLR-2 (toll-like receptor-2) and JAK-2/STAT-3 pathways and significantly inhibit STAT-3 tyrosine phosphorylation within inflammatory ce
STAT3↓,
DR5↑, several studies showed that QC upregulated the death receptor (DR)
P450↓, it hinders the activity of cytochrome P450 (CYP) enzymes in hepatocytes
MMPs↓, QC has also been shown to suppress metastatic protein expression such as MMPs (matrix metalloproteases)
IFN-γ↓, QC is its ability to inhibit inflammatory mediators including IFN-γ, IL-6, COX-2, IL-8, iNOS, TNF-α,
IL6↓,
COX2/PTGS2↓,
IL8↓,
iNOS↓,
TNF-α↓,
cl‑PARP↑, Induced caspase-8, caspase-9, and caspase-3 activation, PARP cleavage, mitochondrial membrane depolarization,
Apoptosis↑, increased apoptosis and p53 expression
P53↑,
Sp1/3/4↓, HT-29 colon cancer cells: decreased the expression of Sp1, Sp3, Sp4 mrna, and survivin,
survivin↓,
TRAILR↑, H460 Increased the expression of TRAILR, caspase-10, DFF45, TNFR 1, FAS, and decreased the expression of NF-κb, ikkα
Casp10↑,
DFF45↑,
TNFR 1↑,
Fas↑,
NF-kB↓,
IKKα↓,
cycD1/CCND1↓, SKOV3 Reduction in cyclin D1 level
Bcl-2↓, MCF-7, HCC1937, SK-Br3, 4T1, MDA-MB-231 Decreased Bcl-2 expression, increasedBax expression, inhibition of PI3K-Akt pathway
BAX↑,
PI3K↓,
Akt↓,
E-cadherin↓, MDA-MB-231 Induced the expression of E-cadherin and downregulated vimentin levels, modulation of β-catenin target genes such as cyclin D1 and c-Myc
Vim↓,
β-catenin/ZEB1↓,
cMyc↓,
EMT↓, MCF-7 Suppressed the epithelial–mesenchymal transition process, upregulated E-cadherin expression, downregulated vimentin and MMP-2 expression, decreased Notch1 expression
MMP2↓,
NOTCH1↓,
MMP7↓, PANC-1, PATU-8988 Decreased the secretion of MMP and MMP7, blocked the STAT3 signaling pathway
angioG↓, PC-3, HUVECs Reduced angiogenesis, increased TSP-1 protein and mrna expression
TSP-1↑,
CSCs↓, PC-3 and LNCaP cells Activated capase-3/7 and inhibit the expression of Bcl-2, surviving and XIAP in CSCs.
XIAP↓,
Snail↓, inhibiting the expression of vimentin, slug, snail and nuclear β-catenin, and the activity of LEF-1/TCF responsive reporter
Slug↓,
LEF1↓,
P-gp/ABCB1↓, MCF-7 and MCF-7/dox cell lines Downregulation of P-gp expression
EGFR↓, MCF-7 and MDA-MB-231 cells Suppressed EGFR signaling and inhibited PI3K/Akt/mTOR/GSK-3β
GSK‐3β↓,
mTOR↓,
RAGE↓, IA Paca-2, BxPC3, AsPC-1, HPAC and PANC1 Silencing RAGE expression
HSP27↓, Breast cancer In vivo NOD/SCID mice Inhibited the overexpression of Hsp27
VEGF↓, QC significantly reversed an elevation in profibrotic markers (VEGF, IL-6, TGF, COL-1, and COL-3)
TGF-β↓,
COL1↓,
COL3A1↓,

916-

QC,

Quercetin and cancer: new insights into its therapeutic effects on ovarian cancer cells

Review,

Ovarian,

COX2/PTGS2↓,
CRP↓,
ER Stress↑, Quercetin can result in stimulate the ER stress pathway that lead to the cause of cell death and apoptosis
Apoptosis↑,
GRP78/BiP↑,
CHOP/DDIT3↑,
p‑STAT3↓, quercetin suppresses STAT3 and PI3K/AKT/mTOR pathways
PI3K↓,
Akt↓,
mTOR↓,
cMyc↓, leading to downregulate the prosurvival cellular proteins expression, including cMyc, cyclin D1, and c-FLIP
cycD1/CCND1↓,
cFLIP↓,
IL6↓, decreased the IL-6 and IL-10 release
IL10↓,

54-

QC,

Quercetin‑3‑methyl ether suppresses human breast cancer stem cell formation by inhibiting the Notch1 and PI3K/Akt signaling pathways

in-vitro,

BC,

MCF7

 0-20 uM

EMT↓, led to the repression of EMT promotion
E-cadherin↑,
Vim↓,
MMP2↓,
NOTCH1↓, This agent also inhibited Notch1 and PI3K/Akt signalin
PI3K/Akt↓,
PI3k/Akt/mTOR↓,
p‑Akt↓,
EZH2↓, Querectin-3-methyl ether downregulates Notch1, PI3K-AKT and EZH2 signals in breast cancer cells
H3K27ac↓, quercetin-3-methyl ether considerably decreased H3K27 methylation
TumCCA↑, cell cycle dysregulation
CSCs↓, which resulted in the downregulation of protein markers associated with cell cycle, apoptosis, stem cell pluripotency, and self-renewal, including CDK1, Cyclin B1, Bcl-xl, Bcl-2, Sox2 and Nanog
CDK1↓,
CycB/CCNB1↓,
Bcl-xL↓,
Bcl-2↓,
Nanog↓,
H3↓, Treatment with quercetin‑3‑methyl ether alone markedly suppressed the levels of tri‑methyl histone H3 (Lys27)

61-

QC,

Midkine downregulation increases the efficacy of quercetin on prostate cancer stem cell survival and migration through PI3K/AKT and MAPK/ERK pathway

in-vitro,

Pca,

PC3

 40 uM

in-vitro,

Pca,

LNCaP

 LNCap and ARPE-19 cells

in-vitro,

Pca,

ARPE-19

  LNCap and ARPE-19 cells

p‑PI3K↓, combined therapy inhibited the phosphorylation of PI3K, AKT and ERK1/2, and reduced the protein expression of p38, ABCG2 and NF-κB.
p‑Akt↓,
p‑ERK↓,
NF-kB↓,
p38↓,
ABCG2↓,
CD44↓, Quercetin alone exhibited significant cytotoxic effects on CD44+/CD133+
CD133↓,
CSCs↓,

63-

QC,

Quercetin facilitates cell death and chemosensitivity through RAGE/PI3K/AKT/mTOR axis in human pancreatic cancer cells

in-vitro,

Pca,

RAGE↓, Silencing RAGE expression by suppressing the PI3K/AKT/mTOR axis
PI3K↓,
mTOR↓,
Akt↓,
Apoptosis↑,
TumAuto↑,
ChemoSen↑, Quercetin facilitates cell death and chemosensitivity through RAGE/PI3K/AKT/mTOR axis in human pancreatic cancer cells

98-

QC,

Quercetin postconditioning attenuates myocardial ischemia/reperfusion injury in rats through the PI3K/Akt pathway

in-vivo,

Stroke,

 rats

*Bcl-2↑,
*BAX↓,
*Bax:Bcl2↓, Que postconditioning significantly decreased Bax expression and increased Bcl-2 expression
*cardioP↑, cardioprotection by activating the PI3K/Akt signaling pathway and modulating the expression of Bcl-2 and Bax proteins.
*Akt↑,
*PI3K↑,
*LDH↓, Que postconditioning reduced the levels of CK (1642.9±194.3 vs 2679.5±194.3 U/L, P<0.05) and LDH (1273.6±176.5 vs 2618±197.7 U/L, P<0.05) compared to the I/R group

39-

QC,

A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells

Analysis,

NA,

ROS↑, production of ROS in both cancer, and cancer stem cells,
GSH↓, By directly reducing the intracellular pool of glutathione (GSH), QC can influence ROS metabolism
IL6↓, QC is its ability to inhibit inflammatory mediators including IFN-γ, IL-6, COX-2, IL-8, iNOS, TNF-α, and many other cancer inflammatory mechanisms
COX2/PTGS2↓,
IL8↓,
iNOS↓,
TNF-α↓,
MAPK↑, quercetin-3-methyl ether stopped the growth of cancer in the esophagus by blocking the Akt/mTOR/P70S6k and MAPK pathways, which are important for the growth of cancer
ERK↑,
SOD↑,
ATP↓,
Casp↑,
PI3K/Akt↓,
mTOR↓,
NOTCH1↓,
Bcl-2↓,
BAX↑,
IFN-γ↓,
TumCP↓, QC directly involves inducing apoptosis and/or the cell cycle arrest process, and also inhibits the propagation of rapidly proliferating cells
TumCCA↑,
Akt↓, quercetin-3-methyl ether stopped the growth of cancer in the esophagus by blocking the Akt/mTOR/P70S6k and MAPK pathways, which are important for the growth of cancer
P70S6K↓,
*Keap1↓,
*GPx↑, inhibiting its negative regulator, Keap1, resulting in Nrf-2 nuclear translocation [86]. This results in the production and activation of enzymes namely GPX, CAT, heme oxygenase 1 (HO-1), peroxiredoxin (PRX)
*Catalase↑,
*HO-1↑,
*NRF2↑,
NRF2↑, The effect of QC on nuclear translocation of Nrf-2 in a time-dependent manner, and increased expression level in HepG2, MgM (malignant mesothelioma) MSTO-211H, and H2452 cells at mRNA and protein quantity has been reported recently
eff↑, quercetin coupled with gold nanoparticles promoted apoptosis by inhibiting the EGFR/P13K/Akt-mediated pathway
HIF-1↓, Quercetin has been shown to suppress the Akt-mTOR pathway and hypoxia-induced factor 1 signaling pathway in gastric cancer cells, resulting in preventative autophagy

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.

86-

QC,

PacT,

Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3)

vitro+vivo,

Pca,

PC3

 25, 50, 75, 100, 125 uM

BAD↑, Quercetin up regulate mRNA and protein levels of Bad
IGFBP3↑,
Cyt‑c↑, Quercetin significantly increases the proapoptotic mRNA levels of Bad, IGFBP-3 and protein levels of Bad, cytochrome C, cleaved caspase-9, caspase-10, cleaved PARP and caspase-3 activity in PC-3 cells
cl‑Casp9↑, cleaved
Casp10↑,
cl‑PARP↑, Quercetin increases protein expression of cytochrome C and PARP
Casp3↑,
IGF-1R↓,
PI3K↓, PI3K expression significantly decreased after quercetin treatment
p‑Akt↓,
cycD1/CCND1↓, protein
IGF-1↓, mRNA levels of IGF-1,IGR-2, IGF-1R
IGF-2↓,
IGF-1R↓,
MMP↓, Apoptosis is confirmed by loss of mitochondrial membrane potential in quercetin treated PC-3 cells.
Apoptosis↑, uercetin treatment has been associated with antiproliferative effects [39] and induction of apop- tosis in cancer cells but not in normal cells [40].
NA?,

95-

QC,

Quercetin, a natural dietary flavonoid, acts as a chemopreventive agent

in-vitro,

Pca,

PC3

 10, 50, 100 uM

p‑ERK↓, ERK1/2
p‑STAT3↓, pSTAT3
p‑Akt↓,
N-cadherin↓,
Vim↓,
cycD1/CCND1↓,
Snail↓,
Slug↓,
Twist↓, mRNA
PCNA↓, simultaneous quercetin supplementation significantly decreased PCNA, N-cadherin, vimentin, and cyclin D1 protein levels compared to chemically induced cancer rats.
EGFR↓, by inhibiting the EGFR signaling pathway and by regulating cell adhesion molecules in Sprague Dawley rats.
chemoPv↑, acts as a chemopreventive agent

92-

QC,

Quercetin Inhibits Angiogenesis Mediated Human Prostate Tumor Growth by Targeting VEGFR- 2 Regulated AKT/mTOR/P70S6K Signaling Pathways

vitro+vivo,

Pca,

HUVECs

 10, 20, 30, 40 umol/L;

vitro+vivo,

Pca,

PC3

 20mg/kg/day

VEGFR2/KDR/Flk1↓, Quercetin treatment inhibited the activation of VEGF-R2 and thereby suppressed the AKT/mTOR/P70S6K mediated angiogenesis signaling pathways.
HemoG↓,
Akt↓, AKT/mTOR/P70S6K↓
mTOR↓,
P70S6K↓,
angioG↓, quercetin is a potent inhibitor of angiogenesis in vitro, ex vivo and in vivo.

79-

QC,

Chemopreventive Effect of Quercetin in MNU and Testosterone Induced Prostate Cancer of Sprague-Dawley Rats

in-vivo,

Pca,

 200 mg/kg/3x/week

 rats

GSH↑, The lipid peroxidation, H2O2, in (MNU+T) treated rats were increased and GSH level was decreased, whereas simultaneous quercetin-treated rats reverted back to normal level
SOD↑,
Catalase↑,
GPx↑, SOD, catalase, GPX, Glutathionereductase, GST activities were significantly decreased in VP & DLP ofcancer-induced rats compared to control. Whereas, simultaneousquercetin supplement showed increased activities. (PDF) Chemopreventive Effect of Que
GSR↑,
IGF-1R↓, IGFIR, AKT, AR, cell proliferative and anti-apoptotic proteins were increased in cancer-induced group whereas supplement of quercetin decreased its expression.
Akt↓,
AR↓, Protein expressions of AR were increased in both VP and DLP of cancer-induced rats and decreasedin quercetin supplemented rats.Fig. 2. Effect of quercetin on mRNA expressions of IGFIR, Bax, Bcl2, Caspase-3 and -8 in VP of cancer-induced male rats.G.
TumCP↓,
lipid-P↓,
H2O2↓,
Raf↓, Raf-1 and pMEK pro-tein expressions were increased significantly in cancer-induced rats compared to control whereas simultaneous quercetin treatment decreased the expressions
p‑MEK↓,
Bcl-2↑, Bcl2, Bcl-xl were significantly increased and apoptotic protein caspase-3,-8,-9 expressions were significantly decreased in cancer-induced rats compared to control in both ventral and dorsolateral prostate. But,this was the other way around when s
Bcl-xL↑,
Casp3↑,
Casp8↑,
Casp9↑,

80-

QC,

Quercetin reverses EGF-induced epithelial to mesenchymal transition and invasiveness in prostate cancer (PC-3) cell line via EGFR/PI3K/Akt pathway

in-vitro,

Pca,

PC3

 25, 50, 75, 100, 125 uM

Vim↓, Quercetin prevented EGF-induced expression of N-cadherin and vimentin and increased the expression of E-cadherin in PC-3 cells
ERK↓,
Snail↓,
Slug↓,
Twist↓,
EGFR↓, quercetin prevents EGF-induced EMT via EGFR/PI3k/Akt/ERK1/2 pathway and by suppressing transcriptional repressors Snail, Slug and Twist in PC-3 cells.
p‑Akt↓,
EGFR↓,
N-cadherin↓,
TumMeta↓, concluded from the present study that quercetin may prevent cancer metastasis by targeting EMT.
EMT↓,

81-

QC,

EGCG,

Enhanced inhibition of prostate cancer xenograft tumor growth by combining quercetin and green tea

in-vivo,

Pca,

 0.2%, 0.4%

COMT↓,
MRP1/ABCC1↓,
Ki-67↓,
Bax:Bcl2↑,
AR↓, significant increase in the inhibition of proliferation, androgen receptor (AR) and phosphatidylinositol 3-kinases (PI3K)/Akt signaling, and stimulation of apoptosis.
Akt↓,
p‑ERK↓, ERK1/2
COMT↓, Increased inhibition of COMT protein and mRNA expression and MRP1 protein expression
eff↑, Enhanced inhibition of prostate cancer xenograft tumor growth by combining quercetin and green tea
chemoPv↑, novel regimen by combining GT and Q to improve chemoprevention in a non-toxic manner and warrant future studies in humans.
BioAv↑, Increased bioavailability and decreased methylation of GTPs

4162-

QC,

Quercetin attenuates cell apoptosis in focal cerebral ischemia rat brain via activation of BDNF-TrkB-PI3K/Akt signaling pathway

in-vivo,

Stroke,

Rats

*neuroP↑, Quercetin significantly improved neurological function, while it decreased the infarct volume and the number of TdT mediated dUTP nick end labeling positive cells in MCAO rats.
*BDNF↑, The protein expression of BDNF, TrkB and p-Akt also increased in the quercetin treated rats.
*TrkB↑,
*p‑Akt↑,

3608-

QC,

Chronic diseases, inflammation, and spices: how are they linked?

Review,

Var,

AntiCan↑, anti-cancer, anti-inflammatory, and anti-oxidant properties of this phytochemical are demonstrated by numerous studies
*Inflam↓,
*antiOx↑,
*NF-kB↓, ability to downregulate NF-κB and MAPK pathways and enhance PI3K/Akt and Nrf2 pathways
*MAPK↓,
*PI3K↑,
*Akt↑,
*NRF2↑,

3603-

QC,

Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus

Review,

AD,

Review,

Diabetic,

*MAPK↓, We speculate that quercetin may have therapeutic applications in T2DM and AD by targeting MAPK signaling,
*neuroP↑, Quercetin has also shown anti-dementia and neuroprotective efficacies in models of dementia/AD and ischemia–reperfusion injury
*ROS↓, mitigating neuronal oxidative stress and neuroinflammation
*Akt↓, MAPK1 (degree = 18), AKT1 (degree = 15), PIK3R1 (degree = 14), IL6 (degree = 13), PRKCB (degree = 12), TNF, VEGFA, EGFR, CASP3, BCL2, and IL1B
*PI3K↓,
*IL6↓,
*TNF-α↓,
*VEGF↓,
*EGFR↓,
*Casp3↓,
*Bcl-2↓,
*IL1β↓,

4787-

QC,

Quercetin: A Phytochemical with Pro-Apoptotic Effects in Colon Cancer Cells

Review,

CRC,

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.

4827-

QC,

CUR,

Synthetic Pathways and the Therapeutic Potential of Quercetin and Curcumin

Review,

Var,

*AntiCan↑, their anti-cancer effects, but also with regard to their anti-diabetic, anti-obesity, anti-inflammatory, and anti-bacterial actions.
*Inflam↓,
*Bacteria↓,
*AntiDiabetic↑,
*ROS↓, suppression of ROS formation via the inhibition of the enzyme activities involved in their production, or via scavenging ROS directly by acting as hydrogen donors; the chelation of the metal ions that induce ROS production;
*SOD↑, quercetin can eliminate free radicals and help maintain a stable redox state in cells by increasing anti-oxidant enzymes, such as superoxide dismutase (SOD), and catalase expressions, as well as the level of reduced glutathione (GSH)
*Catalase↑,
*GSH↑,
*NRF2↑, Quercetin can protect human granulosa cells from oxidative stress by inducing Nrf2 expression at both the gene and protein levels, which in turn induces the anti-oxidant thioredoxin (Trx) system.
*Trx↑,
*IronCh↑, pure curcumin, a metal chelator, directly removes ROS and regulates numerous enzymes.
*MDA↑, It has the potential to reduce the concentration of malondialdehyde (MDA) in serum and increase the total anti-oxidant potential
cycD1/CCND1↓, Cyclin D1 expression was significantly decreased in quercetin-treated ovarian SKOV-3 cells, but not in cisplatin (CDDP)-resistant SKOV3/CDDP cells.
PI3K↓, The levels of PI3K and phospho-Akt were decreased in curcumin-treated SKOV3 cells, which in turn increased caspase-3 and Bax levels.
Casp3↑,
BAX↑,
ChemoSen↑, Curcumin enhanced the efficacy of chemotherapy in colorectal cancer cells.
ROS↑, suggesting that quercetin-induced cytotoxicity and autophagy were initiated by the generation of ROS
eff↑, quercetin or curcumin with chemotherapeutic agents, as shown below, considerably enhances the antitumor potencies of doxorubicin (DOX) and cisplatin.
MMP↓, The synergistic treatment with curcumin and quercetin inhibited the cell proliferation associated with the loss of mitochondrial membrane potential (ΔΨm), the release of cytochrome c, a decrease in AKT and ERK phosphorylation in MGC803 human gastric
Cyt‑c↑,
Akt↓,
ERK↓,

3354-

QC,

Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine

Review,

Var,

*ROS↓, quercetin is the most effective free radical scavenger in the flavonoid family
*IronCh↓, Chelating metal ions: related studies have confirmed that quercetin can induce Cu2+ and Fe2+ to play an antioxidant role through catechol in its structure.
*lipid-P↓, quercetin could inhibit Fe2+-induced lipid peroxidation by binding Fe2+ a
*GSH↑, regulation of glutathione levels to enhance antioxidant capacity.
*NRF2↑, quercetin upregulates the expression of Nrf2 and nuclear transfer by activating the intracellular p38 MAPK pathway, increasing the level of intracellular GSH
TumCCA↑, human leukaemia U937 cells, quercetin induces cell cycle arrest at G2 (late DNA synthesis phase)
ER Stress↑, quercetin can induce ER stress and promote the release of p53, thereby inhibiting the activities of CDK2, cyclin A, and cyclin B, thereby causing MCF-7 breast cancer cells to stagnate in the S phase.
P53↑,
CDK2↓,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓, downregulation of cyclins E and D, PNCA, and Cdk-2 protein expression and increased expressions of p21 and p27
cycD1/CCND1↓,
PCNA↓,
P21↑,
p27/CDKN1B↑,
PI3K↓, quercetin inhibited the PI3K/AKT/mTOR and STAT3 pathways in PEL, which downregulated the expression of survival cell proteins such as c-FLIP, cyclin D1, and cMyc.
Akt↓,
mTOR↓,
STAT3↓, in excess of 20 μM by inhibiting STAT3 signalling
cFLIP↓,
cMyc↓,
survivin↓, Lung cancer [27] ↓ Survivin ↑DR5
DR5↓,
*Inflam↓, Quercetin has been confirmed to be a long-acting anti-inflammatory substance in flavonoids
*IL6↓, inhibit IL-8 is stronger and can inhibit IL-6 and increase cytosolic calcium levels
*IL8↓,
COX2/PTGS2↓, inhibit the enzymes that produce inflammation (cyclooxygenase (COX) and lipoxygenase (LOX))
5LO↓,
*cardioP↑, The protective mechanism of quercetin on the cardiovascular system
*FASN↓, 25 μM, within 30 minutes could inhibit the synthesis of fatty acids.
*AntiAg↑, quercetin helps reduce lipid peroxidation, platelet aggregation, and capillary permeability
*MDA↓, quercetin can decrease the levels of malondialdehyde (MDA)

3353-

QC,

Quercetin triggers cell apoptosis-associated ROS-mediated cell death and induces S and G2/M-phase cell cycle arrest in KON oral cancer cells

in-vitro,

Oral,

KON

 0, 1.5625, 3.125, 6.25, 12.5, 25, 50, 100, and 400 µg/mL

50ug/L @ 72h

in-vitro,

Nor,

MRC-5

tumCV↓, reduced the vitality of KON cells and had minimal effect on MRC cells.
selectivity↑, Owing to the appropriate dosages of quercetin needed to treat these diseases, normal cells do not exhibit any overtly harmful side effects.
TumCCA↑, quercetin increased the percentage of dead cells and cell cycle arrests in the S and G2/M phases.
TumCMig↓, quercetin inhibited KON cells’ capacity for migration and invasion in addition to their effects on cell stability and structure
TumCI↓,
Apoptosis↑, inducing apoptosis and preventing metastasis, quercetin was found to downregulate the expression of BCL-2/BCL-XL while increasing the expression of BAX.
TumMeta↓,
Bcl-2↓,
BAX↑,
TIMP1↑, TIMP-1 expression was upregulated while MMP-2 and MMP-9 were downregulated.
MMP2↓,
MMP9↓,
*Inflam↓, anti-inflammatory, anti-cancer, antibacterial, antifungal, anti-diabetic, antimalarial, neuroprotective, and cardioprotective properties.
*neuroP↑,
*cardioP↑,
p38↓, MCF-7 cells, quercetin successfully decreased the expression of phosphor p38MAPK, Twist, p21, and Cyclin D1
MAPK↓,
Twist↓,
P21↓,
cycD1/CCND1↓,
Casp3↑, directly aided by the significant increase in caspase-3 and − 9 levels and activities
Casp9↑,
p‑Akt↓, High quercetin concentrations also caused an inhibition of Akt and ERK phosphorylation
p‑ERK↓,
CD44↓, reduced cell division and triggered apoptosis, albeit to a lesser degree in CD44+/CD24− cells.
CD24↓,
ChemoSen↑, combination of quercetin and doxorubicin caused G2/M arrest in T47D cells, and to a lesser amount in cancer stem cells (CSCs) that were isolate
MMP↓, (lower levels of ΔΨ m), which is followed by the release of Cyto C, AIF, and Endo G from mitochondria, which causes apoptosis and ultimately leads to cell death.
Cyt‑c↑,
AIF↑,
ROS↑, Compared to the control group, quercetin administration significantly raised ROS levels at 25, 50, 100, 200, and 400 µg/mL.
Ca+2↑, increased production of reactive oxygen species and Ca2+, decreased levels of mitochondrial membrane potential (ΔΨ m),
Hif1a↓, Quercetin treatment resulted in a considerable downregulation of HIF-1α, VEGF, MMP2, and MMP9 mRNA and protein expression levels in HOS cells.
VEGF↓,

3341-

QC,

Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application

Review,

Var,

Review,

Stroke,

*antiOx↑, we highlight the recent advances in the antioxidant activities, chemical research, and medicinal application of quercetin.
*BioAv↑, Moreover, owing to its high solubility and bioavailability,
*GSH↑, Animal and cell studies found that quercetin induces GSH synthesis
*AChE↓, In this way, it has a stronger inhibitory effect against key enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are associated with oxidative properties
*BChE↓,
*H2O2↓, Quercetin has been shown to alleviate the decline of manganese-induced antioxidant enzyme activity, the increase of AChE activity, hydrogen peroxide generation, and lipid peroxidation levels in rats, thereby preventing manganese poisoning
*lipid-P↓,
*SOD↑, quercetin significantly enhanced the expression levels of endogenous antioxidant enzymes such as Cu/Zn SOD, Mn SOD, catalase (CAT), and GSH peroxidase in the hippocampal CA1 pyramidal neurons of animals suffering from ischemic injury.
*SOD2↑,
*Catalase↑,
*GPx↑,
*neuroP↑, Thus, quercetin may be a potential neuroprotective agent for transient ischemia
*HO-1↑, quercetin can promote fracture healing in smokers by removing free radicals and upregulating the expression of heme-oxygenase- (HO-) 1 and superoxide-dismutase- (SOD-) 1, which protects primary human osteoblasts exposed to cigarette smoke
*cardioP↑, Quercetin has also been shown to prevent heart damage by clearing oxygen-free radicals caused by lipopolysaccharide (LPS)-induced endotoxemia.
*MDA↓, quercetin treatment increased the levels of SOD and CAT and reduced the level of MDA after LPS induction, suggesting that quercetin enhanced the antioxidant defense system
*NF-kB↓, quercetin promotes disease recovery by downregulating the expression of NIK and NF-κB including IKK and RelB, and upregulating the expression of TRAF3.
*IKKα↓,
*ROS↓, quercetin controls the development of atherosclerosis induced by a high-fructose diet by inhibiting ROS and enhancing PI3K/AKT.
*PI3K↑,
*Akt↑,
*hepatoP↑, Quercetin exerts antioxidant and hepatoprotective effects against acute liver injury in mice induced by tertiary butyl hydrogen peroxide. T
P53↑, Quercetin prevents cancer development by upregulating p53, which is the most common inactivated tumor suppressor. It also increases the expression of BAX, a downstream target of p53 and a key pro-apoptotic gene in HepG2 cells
BAX↑,
IGF-1R↓, Studies have found that insulin-like growth factor receptor 1 (IGFIR), AKT, androgen receptor (AR), and cell proliferation and anti-apoptotic proteins are increased in cancer, but quercetin supplementation normalizes their expression
Akt↓,
AR↓,
TumCP↓,
GSH↑, Moreover, quercetin significantly increases antioxidant enzyme levels, including GSH, SOD, and CAT, and inhibits lipid peroxides, thereby preventing skin cancer induced by 7,12-dimethyl Benz
SOD↑,
Catalase↑,
lipid-P↓,
*TNF-α↓, Heart: increases TNF-α, and prevents Ca2+ overload-induced myocardial cell injury
*Ca+2↓,

3378-

QC,

CK2 and PI3K are direct molecular targets of quercetin in chronic lymphocytic leukaemia

in-vitro,

AML,

CK2↓, We demonstrated that the activity of protein kinase CK2, which positively triggers PI3K/Akt pathway by inactivating PTEN phosphatase, is inhibited by quercetin
PI3K↓, The combined inhibition of CK2 and PI3K kinase activities by quercetin restored ABT-737 sensitivity and increased lethality in human leukemia cells.
TumCD↑,
Akt↓, Quercetin inhibits the PI3K-Akt-Mcl-1 pathway
Mcl-1↓,
PTEN↑, Inhibition of CK2 can rescue PTEN activity increasing apoptosis in CLL

3369-

QC,

Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects

Review,

Pca,

FAK↓, Quercetin can inhibit HGF-induced melanoma cell migration by inhibiting the activation of c-Met and its downstream Gabl, FAK and PAK [84]
TumCCA↑, stimulation of cell cycle arrest at the G1 stage
p‑pRB↓, mediated through regulation of p21 CDK inhibitor and suppression of pRb phosphorylation resulting in E2F1 sequestering.
CDK2↑, low dose of quercetin has brought minor DNA injury and Chk2 induction
CycB/CCNB1↓, quercetin has a role in the reduction of cyclin B1 and CDK1 levels,
CDK1↓,
EMT↓, quercetin suppresses epithelial to mesenchymal transition (EMT) and cell proliferation through modulation of Sonic Hedgehog signaling pathway
PI3K↓, quercetin on other pathways such as PI3K, MAPK and WNT pathways have also been validated in cervical cancer
MAPK↓,
Wnt↓,
ROS↑, colorectal cancer, quercetin has been shown to suppress carcinogenesis through various mechanisms including affecting cell proliferation, production of reactive oxygen species and expression of miR-21
miR-21↑,
Akt↓, Figure 1 anti-cancer mechanisms
NF-kB↓,
FasL↑,
Bak↑,
BAX↑,
Bcl-2↓,
Casp3↓,
Casp9↑,
P53↑,
p38↑,
MAPK↑,
Cyt‑c↑,
PARP↓,
CHOP/DDIT3↑,
ROS↓,
LDH↑,
GRP78/BiP↑,
ERK↑,
MDA↓,
SOD↑,
GSH↑,
NRF2↑,
VEGF↓,
PDGF↓,
EGF↓,
FGF↓,
TNF-α↓,
TGF-β↓,
VEGFR2/KDR/Flk1↓,
EGFR↓,
FGFR1↓,
mTOR↓,
cMyc↓,
MMPs↓,
LC3B-II↑,
Beclin-1↑,
IL1β↓,
CRP↓,
IL10↓,
COX2/PTGS2↓,
IL6↓,
TLR4↓,
Shh↓,
HER2/EBBR2↓,
NOTCH↓,
DR5↑, quercetin has enhanced DR5 expression in prostate cancer cells
HSP70/HSPA5↓, Quercetin has also suppressed the upsurge of hsp70 expression in prostate cancer cells following heat treatment and enhanced the quantity of subG1 cells
CSCs↓, Quercetin could also suppress cancer stem cell attributes and metastatic aptitude of isolated prostate cancer cells through modulating JNK signaling pathway
angioG↓, Quercetin inhibits angiogenesis-mediated of human prostate cancer cells through negatively modulating angiogenic factors (TGF-β, VEGF, PDGF, EGF, bFGF, Ang-1, Ang-2, MMP-2, and MMP-9)
MMP2↓,
MMP9↓,
IGFBP3↑, Quercetin via increasing the level of IGFBP-3 could induce apoptosis in PC-3 cells
uPA↓, Quercetin through decreasing uPA and uPAR expression and suppressing cell survival protein and Ras/Raf signaling molecules could decrease prostate cancer progression
uPAR↓,
RAS↓,
Raf↓,
TSP-1↑, Quercetin through TSP-1 enhancement could effectively inhibit angiogenesis

3368-

QC,

The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update

Review,

Var,

*Inflam↓, quercetin is known for its anti-inflammatory, antioxidant, and anticancer properties.
*antiOx↑,
*AntiCan↑,
Casp3↓, Quercetin increases apoptosis and autophagy in cancer by activating caspase-3, inhibiting the phosphorylation of Akt, mTOR, and ERK, lessening β-catenin, and stabilizing the stabilization of HIF-1α.
p‑Akt↓,
p‑mTOR↓,
p‑ERK↓,
β-catenin/ZEB1↓,
Hif1a↓,
AntiAg↓, Quercetin have revealed an anti-tumor effect by reducing development of blood vessels. I
VEGFR2/KDR/Flk1↓, decrease tumor growth through targeting VEGFR-2-mediated angiogenesis pathway and suppressing the downstream regulatory component AKT in prostate and breast malignancies.
EMT↓, effects of quercetin on inhibition of EMT, angiogenesis, and invasiveness through the epidermal growth factor receptor (EGFR)/VEGFR-2-mediated pathway in breast cancer
EGFR↓,
MMP2↓, MMP2 and MMP9 are two remarkable compounds in metastatic breast cancer (28–30). quercetin on breast cancer cell lines (MDA-MB-231) and showed that after treatment with this flavonoid, the expression of these two proteinases decreased
MMP↓,
TumMeta↓, head and neck (HNSCC), the inhibitory effect of quercetin on the migration of tumor cells has been shown by regulating the expression of MMPs
MMPs↓,
Akt↓, quercetin by inhibiting the Akt activation pathway dependent on Snail, diminishing the expression of N-cadherin, vimentin, and ADAM9 and raising the expression of E-cadherin and proteins
Snail↓,
N-cadherin↓,
Vim↓,
E-cadherin↑,
STAT3↓, inhibiting STAT3 signaling
TGF-β↓, reducing the expression of TGF-β caused by vimentin and N-cadherin, Twist, Snail, and Slug and increasing the expression of E-cadherin in PC-3 cells.
ROS↓, quercetin exerted an anti-proliferative role on HCC cells by lessening intracellular ROS independently of p53 expression
P53↑, increasing the expression of p53 and BAX in hepatocellular carcinoma (HepG2) cell lines through the reduction of PKC, PI3K, and cyclooxygenase (COX-2)
BAX↑,
PKCδ↓,
PI3K↓,
COX2/PTGS2↓,
cFLIP↓, quercetin by inhibiting PI3K/AKT/mTOR and STAT3 pathways, decreasing the expression of cellular proteins such as c-FLIP, cyclin D1, and c-Myc, as well as reducing the production of IL-6 and IL-10 cytokines, leads to the death of PEL cells
cycD1/CCND1↓,
cMyc↓,
IL6↓,
IL10↓,
Cyt‑c↑, In addition, quercetin induced c-cytochrome-dependent apoptosis and caspase-3 almost exclusively in the HSB2 cell line
TumCCA↑, Exposure of K562 cells to quercetin also significantly raised the cells in the G2/M phase, which reached a maximum peak in 24 hours
DNMTs↓, pathway through DNA demethylation activity, histone deacetylase (HDAC) repression, and H3ac and H4ac enrichment
HDAC↓,
ac‑H3↑,
ac‑H4↑,
Diablo↑, SMAC/DIABLO exhibited activation
Casp3↑, enhanced levels of activated caspase 3, cleaved caspase 9, and PARP1
Casp9↑,
PARP1↑,
eff↑, green tea and quercetin as monotherapy caused the reduction of levels of anti-apoptotic proteins, CDK6, CDK2, CYCLIN D/E/A, BCL-2, BCL-XL, and MCL-1 and an increase in expression of BAX.
PTEN↑, Quercetin upregulates the level of PTEN as a tumor suppressor, which inhibits AKT signaling
VEGF↓, Quercetin had anti-inflammatory and anti-angiogenesis effects, decreasing VGEF-A, NO, iNOS, and COX-2 levels
NO↓,
iNOS↓,
ChemoSen↑, quercetin and chemotherapy can potentiate their effect on the malignant cell
eff↑, combination with hyperthermia, Shen et al. Quercetin is a method used in cancer treatment by heating, and it was found to reduce Doxorubicin hydrochloride resistance in leukemia cell line K562
eff↑, treatment with ellagic acid, luteolin, and curcumin alone showed excellent anticancer effects.
eff↑, co-treatment with quercetin and curcumin led to a reduction of mitochondrial membrane integrity, promotion of cytochrome C release, and apoptosis induction in CML cells
uPA↓, A-549 cells were shown to have reduced mRNA expressions of urokinase plasminogen activator (uPA), Upar, protein expression of CXCR-4, CXCL-12, SDF-1 when quercetin was applied at 20 and 40 mM/ml by real-time PCR.
CXCR4↓,
CXCL12↓,
CLDN2↓, A-549 cells, indicated that quercetin could reduce mRNA and protein expression of Claudin-2 in A-549 cell lines without involving Akt and ERK1/2,
CDK6↓, CDK6, which supports the growth and viability of various cancer cells, was hampered by the dose-dependent manner of quercetin (IC50 dose of QR for A-549 cells is 52.35 ± 2.44 μM).
MMP9↓, quercetin up-regulated the rates of G1 phase cell cycle and cellular apoptotic in both examined cell lines compared with the control group, while it declined the expressions of the PI3K, AKT, MMP-2, and MMP-9 proteins
TSP-1↑, quercetin increased TSP-1 mRNA and protein expression to inhibit angiogenesis,
Ki-67↓, significant reductions in Ki67 and PCNA proliferation markers and cell survival markers in response to quercetin and/or resveratrol.
PCNA↓,
ROS↑, Also, quercetin effectively causes intracellular ROS production and ER stress
ER Stress↑,

Showing Research Papers: 1 to 28 of 28

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 28

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

NA?, 1,

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 2, chemoP↑, 1, chemoPv↑, 2,
Total Targets: 223

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 5, Catalase↑, 4, GPx↑, 2, GSH↑, 4, H2O2↓, 1, HO-1↑, 2, Keap1↓, 1, lipid-P↓, 4, MDA↓, 4, MDA↑, 1, NRF2↑, 5, ROS↓, 7, SOD↑, 3, SOD2↑, 1, Trx↑, 1,

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↓, 1, IronCh↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMP↓, 1, FASN↓, 1, LDH↓, 1, NADPH↓, 1,

Cell Death(tgid=5) ⓘ

Akt↓, 1, Akt↑, 4, p‑Akt↑, 1, BAX↓, 1, Bax:Bcl2↓, 1, Bcl-2↓, 1, Bcl-2↑, 1, Casp3↓, 1, iNOS↓, 1, MAPK↓, 2, MAPK↑, 1, p38↑, 1,

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

PI3K↓, 1, PI3K↑, 4,

Migration(tgid=13) ⓘ

AntiAg↑, 1, Ca+2↓, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

EGFR↓, 1, VEGF↓, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

IKKα↓, 1, IL1β↓, 1, IL6↓, 2, IL8↓, 1, Inflam↓, 5, NF-kB↓, 3, TNF-α↓, 2,

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 1, BChE↓, 1, BDNF↑, 1, TrkB↑, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1, Dose↑, 1,

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 1, IL6↓, 2, LDH↓, 1,

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 2, AntiDiabetic↑, 1, cardioP↑, 4, hepatoP↑, 1, memory↑, 1, neuroP↑, 5, radioP↑, 1,

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1,
Total Targets: 63

Scientific Paper Hit Count for: Akt, PKB-Protein kinase B

28 Quercetin
1 Paclitaxel/Taxol
1 EGCG (Epigallocatechin Gallate)
1 Curcumin

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#:4  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Quercetin / Akt Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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