condition found tbRes List
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


TumCCA, Tumor cell cycle arrest: Click to Expand ⟱
Source:
Type:
Tumor cell cycle arrest refers to the process by which cancer cells stop progressing through the cell cycle, which is the series of phases that a cell goes through to divide and replicate. This arrest can occur at various checkpoints in the cell cycle, including the G1, S, G2, and M phases. S, G1, G2, and M are the four phases of mitosis.
Scientific Papers found: Click to Expand⟱
1997- Myr,  QC,    Inhibition of Mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity
- in-vitro, Lung, A549
TrxR↓, Myricetin and quercetin were found to have strong inhibitory effects on mammalian TrxRs with IC50 values of 0.62 and 0.97 micromol/L, respectively
eff↑, Oxygen-derived superoxide anions enhanced the inhibitory effect whereas anaerobic conditions attenuated inhibition.
TumCCA↑, cell cycle was arrested in S phase by quercetin and an accumulation of cells in sub-G1 was observed in response to myricetin.
eff↓, presence of superoxide dismutase diminished the inhibition dramatically
ROS↑, show that ROS played a critical role in the inhibition of TrxR by flavonoids. ...may occur as a result of their easy oxidization to flavonol semiquinone species.

2343- QC,    Pharmacological Activity of Quercetin: An Updated Review
- Review, Nor, NA
*ROS↓, Quercetin is a potent scavenger for ROS and hence protects the body against oxidative stress
*GSH↓, Studies of animals and cells have shown that the synthesis of GSH is induced by quercetin.
*Catalase↑, increased expression of superoxide dismutase (SOD), catalase (CAT), and GSH has been reported with the pretreatment of quercetin
*SOD↑,
*MDA↓, quercetin supplementation to layer chickens significantly reduced malondialdehyde (MDA) levels in the kidneys, liver, and heart and increased GSH, CAT, and glutathione peroxidase (GSH-Px) activities in the liver, kidney, and heart tissue
*GPx↑,
*Copper↓, In addition, quercetin can exert antioxidant effects by chelating Cu2+ and Fe2+ in its structure with catechol
*Iron↓,
Apoptosis↓, Quercetin inhibits the proliferation of liver cancer cells via induction of apoptosis and cell cycle arrest [43].
TumCCA↑,
MMP2↓, In HSC-6, SCC-9 human oral cancer cell lines, quercetin inhibits cell viability, migration, and invasion, reduces MMP-2 and MMP-9 abundance, downgrades miR-16, and upgrades HOXA10
MMP9↓,
GlucoseCon↓, quercetin inhibits the mobility of cancer cells by inhibiting glucose uptake and lactic acid production and reducing levels of PKM2, GLUT1, and LDHA, which may have a significant role in controlling breast cancer [56].
lactateProd↓,
PKM2↓,
GLUT1↓,
LDHA↓,
ROS↑, Quercetin encapsulated in solid lipid nanoparticles ,MCF-7 and MCF-10A cells, Increase (ROS)

913- QC,    Effects of low dose quercetin: Cancer cell-specific inhibition of cell cycle progression
- in-vitro, BC, SkBr3 - in-vitro, BC, MDA-MB-435
TumCP↓,
TumCCA↑, arrest at the G1 phase
DNAdam↑, mild DNA damage
Chk2↑,
CycB↓, cyclin B1
CDK1↓,
tumCV↓, 94% viability with 10uM
p‑RB1↓, Rb
P21↑,

910- QC,    The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism
tumCV↓,
Apoptosis↑,
PI3k/Akt/mTOR↓, QUE induces cell death by inhibiting PI3K/Akt/mTOR and STAT3 pathways in PEL cells
Wnt/(β-catenin)↓, reducing β-catenin
MAPK↝,
ERK↝, ERK1/2
TumCCA↑, cell cycle arrest at the G1 phase
H2O2↑,
ROS↑,
TumAuto↑,
MMPs↓, Consistently, QUE was able to reduce the protein levels of MMP-2, MMP-9, VEGF and mTOR, and p-Akt in breast cancer cell lines
P53↑,
Casp3↑,
Hif1a↓, by inactivating the Akt-mTOR pathway [64,74] and HIF-1α
cFLIP↓,
IL6↓, QUE decreased the release of interleukin-6 (IL-6) and IL-10
IL10↓,
lactateProd↓,
Glycolysis↓, It is suggested that QUE alters glucose metabolism by inhibiting monocarboxylate transporter (MCT) activity
PKM2↓,
GLUT1↓,
COX2↓,
VEGF↓,
OCR↓,
ECAR↓,
STAT3↓,
MMP2↓, Consistently, QUE was able to reduce the protein levels of MMP-2, MMP-9, VEGF and mTOR, and p-Akt in breast cancer cell lines
MMP9:TIMP1↓,
mTOR↓,

914- QC,    Quercetin and Cancer Chemoprevention
- Review, NA, NA
GSH↓, high Qu concentration, causes a reduction in GSH content
ROS↑, in tumor cells
TumCCA↑, Depending on the cell type and tumor origin, Qu is able to block the cell cycle at G2/M or at the G1/S transition
Ca+2↑, Qu treatment increases cytosolic Ca2+ levels
MMP↓,
Casp3↑,
Casp8↑,
Casp9↑,
β-catenin/ZEB1↓,
AMPKα↑,
ASK1↑,
p38↑,
TRAIL↑, Qu is a potent enhancer of TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, through the induction of the expression of death receptor (DR)-5, a phenomenon that specifically occurs in prostate cancer cells
DR5↑,
cFLIP↓,
Apoptosis↑, tumor cell lines are prone to cell-cycle arrest and apoptosis at Qu concentrations that have no or little effect on non-transformed cells ****

923- QC,    Quercetin as an innovative therapeutic tool for cancer chemoprevention: Molecular mechanisms and implications in human health
- Review, Var, NA
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↓,
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↓, 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↓, 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↓,

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↑,

3368- QC,    The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update
- Review, Var, NA
*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↓, 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↓,
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↓,
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↑,

3369- QC,    Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects
- Review, Pca, NA
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↓, 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↑,
ROS↓,
LDH↑,
GRP78/BiP↑,
ERK↑,
MDA↓,
SOD↑,
GSH↑,
NRF2↑,
VEGF↓,
PDGF↓,
EGF↓,
FGF↓,
TNF-α↓,
TGF-β↓,
VEGFR2↓,
EGFR↓,
FGFR1↓,
mTOR↓,
cMyc↓,
MMPs↓,
LC3B-II↑,
Beclin-1↑,
IL1β↓,
CRP↓,
IL10↓,
COX2↓,
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

3372- QC,  FIS,  KaempF,    Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers
- Review, HNSCC, NA
ROCK1↑, quercetin affects the level of RhoA and NF-κB proteins in SAS cells, and stimulates the expression of RhoA, ROCK1, and NF-κB in SAS cells [53].
TumCCA↓, inhibition of the cell cycle;
HSPs↓, inhibition of heat shock proteins;
RAS↓, inhibition of Ras protein expression.
ROS↑, fisetin induces production of reactive oxygen species (ROS), increases Ca2+ release, and decreases the mitochondrial membrane potential (Ψm) in head and neck neoplastic cells.
Ca+2↑,
MMP↓,
Cyt‑c↑, quercetin increases the expression level of cytochrome c, apoptosis inducing factor and endonuclease G
Endon↑,
MMP9↓, quercetin inhibits MMP-9 and MMP-2 expression and reduces levels of the following proteins: MMP-2, -7, -9 [49,53] and -10
MMP2↓,
MMP7↓,
MMP-10↓,
VEGF↓, as well as VEGF, NF-κB p65, iNOS, COX-2, and uPA, PI3K, IKB-α, IKB-α/β, p-IKKα/β, FAK, SOS1, GRB2, MEKK3 and MEKK7, ERK1/2, p-ERK1/2, JNK1/2, p38, p-p38, c-JUN, and pc-JUN
NF-kB↓,
p65↓,
iNOS↓,
COX2↓,
uPA↓,
PI3K↓,
FAK↓,
MEK↓,
ERK↓,
JNK↓,
p38↓,
cJun↓,
FOXO3↑, Quercetin causes an increase in the level of FOXO1 protein both in a dose- and time-dependent way; however, it does not affect changes in expression of FOXO3a

3343- QC,    Quercetin, a Flavonoid with Great Pharmacological Capacity
- Review, Var, NA - Review, AD, NA - Review, Arthritis, NA
*antiOx↑, Quercetin has a potent antioxidant capacity, being able to capture reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive chlorine species (ROC),which act as reducing agents by chelating transition-metal ions.
*ROS↓, Quercetin is a potent scavenger of reactive oxygen species (ROS), protecting the organism against oxidative stress
*angioG↓,
*Inflam↓, anti-inflammatory properties; the ability to protect low-density lipoprotein (LDL) oxidation, and the ability to inhibit angiogenesis;
*BioAv↓, It is known that the bioavailability of quercetin is usually relatively low (0.17–7 μg/mL), less than 10% of what is consumed, due to its poor water solubility (hydrophobicity), chemical stability, and absorption profile.
*Half-Life↑, their slow elimination since their half-life ranges from 11 to 48 h, which could favor their accumulation in plasma after repeated intakes
*GSH↑, Animal and cell studies have demonstrated that quercetin induces the synthesis of GSH
*SOD↑, increase in the expression of superoxide dismutase (SOD), catalase (CAT), and GSH with quercetin pretreatment
*Catalase↑,
*Nrf1↑, quercetin accomplishes this process involves increasing the activity of the nuclear factor erythroid 2-related factor 2 (NRF2), enhancing its binding to the ARE, reducing its degradation
*BP↓, quercetin has been shown to inhibit ACE activity, reducing blood pressure
*cardioP↑, quercetin has positive effects on cardiovascular diseases
*IL10↓, Under the influence of quercetin, the levels of interleukin 10 (IL-10), IL-1β, and TNF-α were reduced.
*TNF-α↓,
*Aβ↓, quercetin’s ability to modulate the enzyme activity in clearing amyloid-beta (Aβ) plaques, a hallmark of AD pathology.
*GSK‐3β↓, quercetin can inhibit the activity of glycogen synthase kinase 3β,
*tau↓, thus reducing tau aggregation and neurofibrillary tangles in the brain
*neuroP↑,
*Pain↓, quercetin reduces pain and inflammation associated with arthritis
*COX2↓, quercetin included the inhibition of oxidative stress, production of cytokines such as cyclooxygenase-2 (COX-2) and proteoglycan degradation, and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) (Nrf2/HO-1)
*NRF2↑,
*HO-1↑,
*IL1β↓, Mechanisms included decreased levels of TNF-α, IL-1β, IL-17, and monocyte chemoattractant protein-1 (MCP-1)
*IL17↓,
*MCP1↓,
PKCδ↓, studies with human leukemia 60 (HL-60) cells report that concentrations between 20 and 30 µM are sufficient to exert an inhibitory effect on cytosolic PKC activity and membrane tyrosine protein kinase (TPK) activity.
ERK↓, 50 µM resulted in the blockade of the extracellular signal-regulated kinases (ERK1/2) pathway
BAX↓, higher doses (75–100 µM) were used, as these doses reduced the expression of proapoptotic factors such as Bcl-2-associated X protein (Bax) and caspases 3 and 9
cMyc↓, induce apoptosis at concentrations of 80 µM and also causes a downregulation of cellular myelocytomatosis (c-myc) and Kirsten RAt sarcoma (K-ras) oncogenes
KRAS↓,
ROS↓, compound’s antioxidative effect changes entirely to a prooxidant effect at high concentrations, which induces selective cytotoxicity
selectivity↑, On the other hand, when noncancerous cells are exposed to quercetin, it exerts cytoprotective effects;
tumCV↓, decrease cell viability in human glioma cultures of the U-118 MG cell line as well as an increase in death by apoptosis and cell arrest at the G2 checkpoint of the cell cycle.
Apoptosis↑,
TumCCA↑,
eff↑, quercetin combined with doxorubicin can induce multinucleation of invasive tumor cells, downregulate P-glycoprotein (P-gp) expression, increase cell sensitivity to doxorubicin,
P-gp↓,
eff↑, resveratrol, quercetin, and catechin can effectively block the cell cycle and reduce cell proliferation in vivo
eff↑, cotreatment with epigallocatechin gallate (EGCG) inhibited catechol-O-methyltransferase (COMT) activity, decreasing COMT protein content and thereby arresting the cell cycle of PC-3 human prostate cancer cells
eff↑, synergistic treatment of tamoxifen and quercetin was also able to inhibit prostate tumor formation by regulating angiogenesis
eff↑, coadministration of 2.5 μM of EGCG, genistein, and quercetin suppressed the cell proliferation of a prostate cancer cell line (CWR22Rv1) by controlling androgen receptor and NAD (P)H: quinone oxidoreductase 1 (NQO1) expression
CycB↓, It can also downregulate cyclin B1 and cyclin-dependent kinase-1 (CDK-1),
CDK1↓,
CDK4↓, quercetin causes a decrease in cyclins D1/Cdk4 and E/Cdk2 and an increase in p21 in vascular smooth muscle cells
CDK2↓,
TOP2↓, quercetin is known to be a potent inhibitor of topoisomerase II (TopoII), a cell cycle-associated enzyme necessary for DNA replication
Cyt‑c↑, quercetin can induce apoptosis (cell death) through caspase-3 and caspase-9 activation, cytochrome c release, and poly ADP ribose polymerase (PARP) cleavage
cl‑PARP↑,
MMP↓, quercetin induces the loss of mitochondrial membrane potential, leading to the activation of the caspase cascade and cleavage of PARP.
HSP70/HSPA5↓, apoptotic effects of quercetin may result from the inhibition of HSP kinases, followed by the downregulation of HSP-70 and HSP-90 protein expression
HSP90↓,
MDM2↓, (MDM2), an onco-protein that promotes p53 destruction, can be inhibited by quercetin
RAS↓, quercetin can prevent Ras proteins from being expressed. In one study, quercetin was found to inhibit the expression of Harvey rat sarcoma (H-Ras), K-Ras, and neuroblastoma rat sarcoma (N-Ras) in human breast cancer cells,
eff↑, there was a substantial difference in EMT markers such as vimentin, N-cadherin, Snail, Slug, Twist, and E-cadherin protein expression in response to AuNPs-Qu-5, inhibiting the migration and invasion of MCF-7 and MDA-MB cells

3346- QC,    Regulation of the Intracellular ROS Level Is Critical for the Antiproliferative Effect of Quercetin in the Hepatocellular Carcinoma Cell Line HepG2
- in-vitro, Liver, HepG2 - in-vitro, Liver, HUH7
TumCCA↑, can induce the cell cycle arrest and apoptosis of hepatocellular carcinoma (HCC) cells by the stabilization or induction of p53
Apoptosis↑,
P53↑,
TumCP↓, quercetin reduced the proliferation of HepG2 cells significantly, but not Huh7 cells
ROS↓, Interestingly, it was found that quercetin down-regulated the intracellular ROS level of HepG2 cells, but not that of Huh7 cells.
antiOx↑, quercetin is useful for HCC treatment as an antioxidant.
HO-1↑, The expression of p53 and HO-1 was upregulated by quercetin after 12 and 24 h, respectively.
CDK1↓, The expression of p53 and HO-1 was increased but that of CHK1 was decreased in response to the increase in quercetin up to 100 μM.

3352- QC,    A review of quercetin: Antioxidant and anticancer properties
- Review, Var, NA
*antiOx↑, Quercetin is considered to be a strong antioxidant due to its ability to scavenge free radicals and bind transition metal ions. T
*lipid-P↓, properties of quercetin allow it to inhibit lipid peroxidation
*TNF-α↓, Quercetin significantly inhibited TNF-α production and gene expression in a dose-dependent manner
*NF-kB↓, inhibiting the activation of NF-κβ,
*COX2↓, Quercetin also inhibits the enzymes cyclooxygenase
*IronCh↑, Quercetin also chelates ions of transition metals such as iron which can initiate the formation of oxygen free radicals
P53↓, Quercetin (248 microM) was found to down regulate expression of mutant p53 protein to nearly undetectable levels in human breast cancer cell lines.
TumCCA↑, Quercetin has been found to arrest human leukemic T-cells in the late G1 phase of the cell cycle.
HSPs↓, Quercetin has been found to inhibit production of heat shock proteins in several malignant cell lines, including breast cancer,[52] leukemia,[53] and colon cancer.[
P21↓, Quercetin (10 microM) has been found to inhibit the expression of the p21-ras oncogene in cultured colon cancer cell lines
RAS↓,
ER(estro)↑, Quercetin has been shown to induce ER II expression in both type I estrogen receptor positive (ER+) and type I estrogen receptor negative (ER-) human breast cancer cells
OS?, Animals treated daily with 40 mg/kg quercetin had a 20-percent increase in life span, while those treated with 160 mg/kg rutin had a 50% increase in life span.

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 - 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↓,
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↓,

3354- QC,    Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine
- Review, Var, NA
*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↓,
CycB↓,
cycE↓, downregulation of cyclins E and D, PNCA, and Cdk-2 protein expression and increased expressions of p21 and p27
cycD1↓,
PCNA↓,
P21↑,
p27↑,
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↓, 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)

36- QC,    Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression-independent manner in HPV-positive human cervical cancer-derived cells
- in-vitro, Cerv, HeLa - in-vitro, Cerv, SiHa
P53↑,
P21↑,
BAX↑,
Casp3↑,
Casp7↑,
TumCCA↑, G2 phase arrest
ROS↑, high concentrations (>40 µM) is able to act as a prooxidant

39- QC,    A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells
- Analysis, NA, 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↓,
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


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 17

Results for Effect on Cancer/Diseased Cells:
5LO↓,1,   AIF↑,1,   Akt↓,5,   p‑Akt↓,2,   AMPKα↑,1,   angioG↓,2,   AntiAg↓,1,   antiOx↑,1,   Apoptosis↓,1,   Apoptosis↑,7,   ASK1↑,1,   ATP↓,1,   Bak↑,1,   BAX↓,1,   BAX↑,6,   Bax:Bcl2↑,1,   Bcl-2↓,4,   Beclin-1↑,1,   Ca+2↑,3,   Ca+2↝,1,   Casp↑,1,   Casp10↑,1,   Casp3↓,2,   Casp3↑,6,   cl‑Casp3↑,1,   Casp7↑,1,   Casp8↑,2,   Casp9↑,5,   cl‑Casp9↑,1,   CD24↓,1,   CD44↓,1,   CDK1↓,4,   CDK2↓,2,   CDK2↑,1,   CDK4↓,1,   CDK6↓,1,   cFLIP↓,4,   ChemoSen↑,2,   Chk2↑,1,   CHOP↑,1,   cJun↓,1,   CLDN2↓,1,   cMyc↓,5,   COL1↓,1,   COL3A1↓,1,   COX2↓,7,   CRP↓,1,   CSCs↓,2,   CXCL12↓,1,   CXCR4↓,1,   cycA1↓,1,   CycB↓,4,   cycD1↓,4,   cycE↓,1,   Cyt‑c↑,5,   DFF45↑,1,   Diablo↑,1,   DNAdam↑,2,   DNMTs↓,1,   DR5↓,1,   DR5↑,3,   E-cadherin↓,1,   E-cadherin↑,1,   ECAR↓,1,   eff↓,1,   eff↑,12,   EGF↓,1,   EGFR↓,3,   EMT↓,3,   Endon↑,1,   ER Stress↑,2,   ER(estro)↑,1,   ERK↓,2,   ERK↑,2,   ERK↝,1,   p‑ERK↓,2,   FAK↓,2,   Fas↑,1,   FasL↑,1,   FGF↓,1,   FGFR1↓,1,   FOXO3↑,1,   GlucoseCon↓,1,   GLUT1↓,2,   Glycolysis↓,1,   GRP78/BiP↑,1,   GSH↓,3,   GSH↑,1,   GSK‐3β↓,1,   H2O2↑,1,   ac‑H3↑,1,   ac‑H4↑,1,   HDAC↓,1,   HER2/EBBR2↓,1,   HIF-1↓,1,   Hif1a↓,3,   HO-1↑,2,   HSP27↓,1,   HSP70/HSPA5↓,2,   HSP90↓,1,   HSPs↓,2,   IFN-γ↓,2,   IGFBP3↑,1,   IKKα↓,1,   IL10↓,3,   IL1β↓,1,   IL6↓,5,   IL8↓,2,   Inflam↓,1,   iNOS↓,4,   JNK↓,1,   Ki-67↓,1,   KRAS↓,1,   lactateProd↓,2,   LC3B-II↑,1,   LDH↑,1,   LDHA↓,1,   LEF1↓,1,   MAPK↓,2,   MAPK↑,2,   MAPK↝,1,   MDA↓,1,   MDM2↓,1,   MEK↓,1,   MGMT↓,1,   miR-21↑,1,   MMP↓,7,   MMP-10↓,1,   MMP2↓,7,   MMP7↓,2,   MMP9↓,5,   MMP9:TIMP1↓,1,   MMPs↓,4,   mTOR↓,5,   p‑mTOR↓,1,   N-cadherin↓,1,   NF-kB↓,3,   NO↓,1,   NOTCH↓,1,   NOTCH1↓,2,   NRF2↑,2,   OCR↓,1,   OS?,1,   other↓,1,   P-gp↓,2,   P21↓,2,   P21↑,3,   p27↑,1,   p38↓,2,   p38↑,2,   P450↓,1,   P53↓,1,   P53↑,7,   p65↓,1,   P70S6K↓,1,   PARP↓,1,   cl‑PARP↑,3,   PARP1↑,1,   PCNA↓,2,   PDGF↓,1,   PI3K↓,5,   PI3K/Akt↓,1,   PI3k/Akt/mTOR↓,1,   PKCδ↓,2,   PKM2↓,2,   p‑pRB↓,1,   PTEN↑,1,   Raf↓,1,   RAGE↓,1,   RAS↓,4,   p‑RB1↓,1,   ROCK1↑,1,   ROS↓,4,   ROS↑,12,   selectivity↑,2,   Shh↓,1,   Slug↓,1,   Snail↓,2,   SOD↑,2,   Sp1/3/4↓,1,   STAT3↓,4,   survivin↓,2,   TGF-β↓,3,   TIMP1↑,1,   TIMP2↑,1,   TLR4↓,1,   TNF-α↓,3,   TNFR 1↑,1,   TOP2↓,1,   TRAIL↑,1,   TRAILR↑,1,   TrxR↓,1,   TSP-1↑,3,   TumAuto↑,1,   TumCCA↓,1,   TumCCA↑,16,   TumCG↓,1,   TumCI↓,1,   TumCMig↓,2,   TumCP↓,3,   tumCV↓,4,   TumMeta↓,2,   Twist↓,1,   uPA↓,3,   uPAR↓,1,   VEGF↓,6,   VEGFR2↓,2,   Vim↓,2,   Wnt↓,1,   Wnt/(β-catenin)↓,1,   XIAP↓,1,   β-catenin/ZEB1↓,3,   γH2AX↑,1,  
Total Targets: 213

Results for Effect on Normal Cells:
angioG↓,1,   AntiAg↑,1,   AntiCan↑,1,   antiOx↑,3,   Aβ↓,1,   BioAv↓,1,   BP↓,1,   cardioP↑,3,   Catalase↑,3,   Copper↓,1,   COX2↓,2,   FASN↓,1,   GPx↑,2,   GSH↓,1,   GSH↑,2,   GSK‐3β↓,1,   Half-Life↑,1,   HO-1↑,2,   IL10↓,1,   IL17↓,1,   IL1β↓,1,   IL6↓,1,   IL8↓,1,   Inflam↓,4,   Iron↓,1,   IronCh↓,1,   IronCh↑,1,   Keap1↓,1,   lipid-P↓,2,   MCP1↓,1,   MDA↓,2,   neuroP↑,2,   NF-kB↓,1,   Nrf1↑,1,   NRF2↑,4,   Pain↓,1,   ROS↓,4,   SOD↑,2,   tau↓,1,   TNF-α↓,2,  
Total Targets: 40

Scientific Paper Hit Count for: TumCCA, Tumor cell cycle arrest
17 Quercetin
1 Myricetin
1 Fisetin
1 Kaempferol
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:140  Target#:322  State#:%  Dir#:%
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