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


β-catenin/ZEB1, β-catenin/ZEB1: Click to Expand ⟱
Source: HalifaxProj (inactivate)
Type:
β-catenin and ZEB1 are two important proteins that play significant roles in cancer biology, particularly in the processes of cell adhesion, epithelial-mesenchymal transition (EMT), and tumor progression.
β-catenin is a key component of the Wnt signaling pathway, which is crucial for cell proliferation, differentiation, and survival. It also plays a role in cell-cell adhesion by linking cadherins to the actin cytoskeleton.
Role in Cancer: ZEB1 is often upregulated in cancer and is associated with increased invasiveness and metastasis. It can repress epithelial markers (like E-cadherin) and promote mesenchymal markers (like N-cadherin and vimentin), facilitating the transition to a more aggressive cancer phenotype.

(MMP)-2 and MMP-9, which are the down-stream targets of β-catenin and play a crucial role in cancer cell metastasis.
Scientific Papers found: Click to Expand⟱
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↓,

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↑,

60- QC,  EGCG,  isoFl,  isoFl,  isoFl  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, pCSCs
Casp3↑,
Casp7↑,
Bcl-2↓,
survivin↓,
XIAP↓,
EMT↓,
Slug↓,
Snail↓,
β-catenin/ZEB1↓,
LEF1↓, LEF-1/TCF

76- QC,    Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy
- in-vitro, Pca, PC3
aSmase↝,
Diablo↝,
Fas↝,
Hsc70↝,
Hif1a↝,
Mcl-1↝,
HSP90↝,
FLT4↝,
EphB4↝,
DNA-PK↝,
PARP1↝,
ATM↝,
XIAP↝,
PLC↝,
GnT-V↝,
heparanase↝,
NM23↝,
CSR1↝,
SPP1↝,
DNMT1↝,
HDAC4↝,
CXCR4↝,
β-catenin/ZEB1↝,
FBXW7↝,
AMACR↝,
cycD1↝,
IGF-1R↝,
IMPDH1↝,
IMPDH2↝,
HEC1↝,
NHE1↝,
NOS2↝,

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↑,
Casp7↑,
Bcl-2↓,
survivin↓,
XIAP↓,
EMT↓,
Vim↓,
Slug↓,
Snail↓,
β-catenin/ZEB1↓,
LEF1↓, LEF1/TCF
TCF↓, LEF1/TCF
Nanog↓,

46- QC,    Quercetin, but Not Its Glycosidated Conjugate Rutin, Inhibits Azoxymethane-Induced Colorectal Carcinogenesis in F344 Rats
- in-vitro, Colon, F344
β-catenin/ZEB1↓,

85- QC,    Quercetin inhibits invasion, migration and signalling molecules involved in cell survival and proliferation of prostate cancer cell line (PC-3)
- in-vitro, Pca, PC3
uPA↓,
uPAR↓,
EGFR↓,
NRAS↓,
Jun↓,
NF-kB↓,
β-catenin/ZEB1↓,
p38↑,
MAPK↑,
cJun↓,
cFos↓,
Raf↓, Raf-1

87- QC,    Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways
- in-vitro, Pca, LNCaP - in-vitro, Pca, DU145 - in-vitro, Pca, PC3
ROS⇅,
BAX↑, quercetin treatment increased BAX levels
PUMA⇅,
β-catenin/ZEB1↓,
Shc↓,
TAp63α↑, DU-145
MAPK↑, DU-145 DU-145
p‑p42↑,
p‑p44↑,
BIM↑, . In androgen-independent PCa cells with mutated p53 (DU-145), quercetin treatment increases cellular BAX levels whereas PUMA and BIM increased


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Results for Effect on Cancer/Diseased Cells:
Akt↓,2,   p‑Akt↓,1,   AMACR↝,1,   AMPKα↑,1,   angioG↓,1,   AntiAg↓,1,   Apoptosis↑,2,   ASK1↑,1,   aSmase↝,1,   ATM↝,1,   BAX↑,3,   Bcl-2↓,3,   BIM↑,1,   Ca+2↑,1,   Ca+2↝,1,   Casp10↑,1,   Casp3↓,1,   Casp3↑,5,   Casp7↑,2,   Casp8↑,2,   Casp9↑,3,   CDK6↓,1,   cFLIP↓,2,   cFos↓,1,   ChemoSen↑,1,   cJun↓,1,   CLDN2↓,1,   cMyc↓,2,   COL1↓,1,   COL3A1↓,1,   COX2↓,2,   CSCs↓,1,   CSR1↝,1,   CXCL12↓,1,   CXCR4↓,1,   CXCR4↝,1,   cycD1↓,2,   cycD1↝,1,   Cyt‑c↑,1,   DFF45↑,1,   Diablo↑,1,   Diablo↝,1,   DNA-PK↝,1,   DNMT1↝,1,   DNMTs↓,1,   DR5↑,2,   E-cadherin↓,1,   E-cadherin↑,1,   eff↑,4,   EGFR↓,3,   EMT↓,4,   EphB4↝,1,   ER Stress↑,1,   p‑ERK↓,1,   Fas↑,1,   Fas↝,1,   FBXW7↝,1,   FLT4↝,1,   GnT-V↝,1,   GSH↓,2,   GSK‐3β↓,1,   ac‑H3↑,1,   ac‑H4↑,1,   HDAC↓,1,   HDAC4↝,1,   HEC1↝,1,   heparanase↝,1,   Hif1a↓,1,   Hif1a↝,1,   HO-1↑,1,   Hsc70↝,1,   HSP27↓,1,   HSP90↝,1,   IFN-γ↓,1,   IGF-1R↝,1,   IKKα↓,1,   IL10↓,1,   IL6↓,2,   IL8↓,1,   IMPDH1↝,1,   IMPDH2↝,1,   Inflam↓,1,   iNOS↓,2,   Jun↓,1,   Ki-67↓,1,   LEF1↓,3,   MAPK↑,2,   Mcl-1↝,1,   MMP↓,3,   MMP2↓,2,   MMP7↓,1,   MMP9↓,1,   MMPs↓,2,   mTOR↓,1,   p‑mTOR↓,1,   N-cadherin↓,1,   Nanog↓,1,   NF-kB↓,2,   NHE1↝,1,   NM23↝,1,   NO↓,1,   NOS2↝,1,   NOTCH1↓,1,   NRAS↓,1,   other↓,1,   P-gp↓,1,   p38↑,2,   p‑p42↑,1,   p‑p44↑,1,   P450↓,1,   P53↑,2,   cl‑PARP↑,1,   PARP1↑,1,   PARP1↝,1,   PCNA↓,1,   PI3K↓,2,   PKCδ↓,1,   PLC↝,1,   PTEN↑,1,   PUMA⇅,1,   Raf↓,1,   RAGE↓,1,   ROS↓,1,   ROS↑,3,   ROS⇅,1,   Shc↓,1,   Slug↓,3,   Snail↓,4,   Sp1/3/4↓,1,   SPP1↝,1,   STAT3↓,2,   survivin↓,3,   TAp63α↑,1,   TCF↓,1,   TGF-β↓,2,   TNF-α↓,1,   TNFR 1↑,1,   TRAIL↑,1,   TRAILR↑,1,   TSP-1↑,2,   TumCCA↑,3,   TumMeta↓,1,   uPA↓,2,   uPAR↓,1,   VEGF↓,2,   VEGFR2↓,1,   Vim↓,3,   XIAP↓,3,   XIAP↝,1,   β-catenin/ZEB1↓,8,   β-catenin/ZEB1↝,1,  
Total Targets: 151

Results for Effect on Normal Cells:
AntiCan↑,1,   antiOx↑,1,   Inflam↓,1,   NRF2↑,1,   ROS↓,1,  
Total Targets: 5

Scientific Paper Hit Count for: β-catenin/ZEB1, β-catenin/ZEB1
9 Quercetin
3 isoflavones
2 EGCG (Epigallocatechin Gallate)
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:140  Target#:342  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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