| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-1023 | |
| Phytochemical name or plant extracts | Quercetin | |
| PMID | 28504248 | |
| Literature evidence | In the current study, we characterized TL-2-8, a quercetin derivative, as a novel anticancer agent in vitro and in vivo. | |
| IUPAC name | 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one | |
| Phytochemicals’ class or type of plant extracts | Flavonoid | |
| Source of phytochemicals or plant Extracts | Melia azedarach | |
| Geographical availability | Assam, Bangladesh, Cambodia, China North-Central, China South-Central, China Southeast, East Himalaya, Hainan, India, Jawa, Laos, Lesser Sunda Is., Nepal, New Guinea, New South Wales, Northern Territory, Philippines, Queensland, Solomon Is., Sri Lanka, Sumatera, Taiwan, Thailand, Vietnam, West Himalaya, Western Australia | |
| Plant parts | Leaves | |
| Other cancers | Breast cancer, Liver cancer, Cervical Cancer, Larynx cancer, Myosarcoma, Ovarian cancer, Lymphoma, Colorectal cancer | |
| Target gene or protein | PTEN, CYP1B1, EGFR, AKR1C3, PIP, SULT1E1, CDK6, STAT-3,UCA1, CAT, Bcl-2, EGFR, RRM2B, CYP3A4, POTEE, Bax, FAS, MMP2, MMP9, MYC, CASP3, CCND1, CD34, CDK2, CXCL10, CXCL11, DVL2, HSF2, RRM2B, PIG8, CD95, PIDD, Tp53INP, Noxa, p21, PUMA, AMPK, COX-2, PI, HER-2, VEGFR-2, PI3K, AKT, PKB, CYP1A1, CYP1B1 | |
| Gene or Protein evidence | Quercetin can increase PTEN and decrease lipid peroxides in PBMCs levels, quercetin and glabrol showed inhibition of CYP1B1 in live cell assay with IC50 values of 2.2 and 15 µM, respectively. Quercetin was used as positive control, and strong binding energy of -7.54 kcal/mol with EGFR is in accordance with experimental evidence. Quercetin and genistein are able to inhibit PI and PIP kinase activities and reduce IP3 concentration in vivo and in tissue culture systems. The combination of docetaxel (7 nM) and quercetin (95 μM) displayed the greatest synergistic effects with a combination index value of 0.76 accompanied by the up regulation of p53 and a significant increase in BAX level, as well as decrease in the levels of BCL2, pERK1/2, AKT, and STAT3 proteins. Quercetin inhibited MMP-9 secretion and decreased the nuclear translocation of STAT3, Altered cellular proliferation was observed in MCF-7 cells stably expressing SULT1E1 upon treatment with chrysin, quercetin, or resveratrol, thus suggesting inactivation of these compounds by SULT1E1. Quercetin induces apoptosis, by decreasing the production of reactive oxygen species and CDK6 expression, quercetin suppresses COX-2 expression by inhibiting the p300 signaling and blocking the binding of multiple transactivators to COX-2 promoter, while quercetin treatment inhibited HSF2 expression, it only slightly affected HSF1 expression in breast cancer cells, curcumin and quercetin in melanoma cells, A375, suggested that inhibition of cell proliferation occurred through down-regulation of Wnt/β-catenin signaling pathway proteins, DVL2, β-catenin, cyclin D1, Cox2, and Axin2, we demonstrate that this elevation of intracellular calcium modulates p53 activity and the subsequent transcription of several pro-apoptotic genes encoding PIG8, CD95, PIDD, TP53INP, RRM2B, Noxa, p21 and PUMA. Among the top-hit phytochemicals docked from H. cordata, the β-sitosterol and Quercetin showed highest binding affinity towards HER2 and VEGFR2 receptors using both hydrogen and hydrophobic interactions. The antiproliferative effect of Quercetin in cancer cells is mediated via inhibition of the PI3K-Akt/PKB pathway The present study aimed to characterize the metabolism and further antiproliferative activity of the hydroxylated flavonoids apigenin, luteolin, scutellarein, kaempferol and quercetin in CYP1 recombinant enzymes and in the CYP1 expressing cell lines MCF7 and MDA-MB-468, respectively. Taken collectively, the data demonstrate that the metabolism of hydroxylated flavonoids by cytochrome P450 CYP1 enzymes, notably CYP1A1 and CYP1B1, can enhance their antiproliferative activity in breast cancer cells. | |
| Target pathways | Exhibits cytotoxic effects by affecting protein-kinase-C-dependent signal pathways and by cell cycle regulation Modification of Foxo3a signaling in triple-negative breast cancer cells. Osteosarcoma, Colon cancer Curcumin and quercetin synergistically modulate Wnt/β-catenin signaling and apoptotic pathways in A375 cells Exerts inhibiting effect on cell mobility and glycolysis through Akt-mTOR pathway mediated autophagy induction Modulates PI3K and PKC signaling in lymphoma as well as hepatocellular carcinoma Induces apoptosis by direct activation of the caspase cascade through the mitochondrial pathway in MCF-7 cells Activates AMPK and causes a decrease in COX-2 expression in MCF breast cancer cell lines and HT-29 colon cancer cells Inhibits the downstream survival PI3K-Akt signaling pathway in Her-2/neu-overexpressing breast cancer SK-Br3 cells, decreases the level of Her-2/neu protein Causes inhibition of the PI3K-Akt/PKB pathway Activates transcription 3 signaling in HER2-overexpressing BT-474 breast cancer cells Causes upregulation of FOXO1 (forkhead box O1) and NF-κBIA (IkappaBalpha), thus activating apoptosis and potentially inhibiting NF-κB (nuclear factor kappaB) activity. Induces a G protein-mediated calcium pathway activating p53 in cancer cells Induces apoptosis in breast cancer cells through suppression of Twist via p38MAPK pathway Causes induction of an ROS-dependent apoptosis pathway in MCF-7 cells | |
| IC50 | 18.288382 ± 0.12 µg/ml against MDA-MB-231 18.1 µM against MDA-MB-468 37μM against MCF-7 | |
| Potency | Quercetin modulates a number of important proteins in cellular signal transduction pathways that are linked to processes involved in cell death and cell survival or cell proliferation | |
| Cell line/ mice model | HeLa, MDA-MB-231, HEP-2, RD, MCF-7, HepG-2, HCT-116, HeLa, CYP1B1, T47D, 143B, HT - 29, MDA-MB-231 - estrogen-negative breast cancer, MDA-MB-435, MDA-MB-468, HCC-38, BT-474, SK-Br3, TAMR-MCF-7, C6 and COLO-205,KBCHR8-5, DLD-1, DLD-1 human colorectal cancer xenograft model in nude mice, NUDE MICE created from green fluorescent protein-tagged MDA-MB-435 bone metastatic variant | |
| Additional information | Increases cell apoptosis and inhibits cell cycle progression Causes decreased levels of Bcl-2 protein and DeltaPsi(m) and increased activations of caspase-6, -8 and -9 Induces growth inhibition, G2/M phase arrest, and apoptosis in the 143B osteosarcoma cell line Activates AMPK in MCF breast cancer cell lines and HT-29 colon cancer cells, causes decrease in COX-2 expression. Reduces MMP-3 activity in a dose-dependent manner Induces INXS upregulation and UCA1 downregulation in the MCF-7 cell line Increases connexin43 (Cx43) levels and suppresses MDA-MB-231 cell proliferation Increases Bax expression but decreases Bcl-2 expression, cleaves caspase-3 and increases PARP expression in MDA-MB-453 cells Down-regulates the expression of cell migration marker proteins, such as matrix metalloproteinase 2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF), suppresses tumor growth and metastasis, inhibit glycolysis and induce autophagy through the inhibition of p-AKT/AKT (IN VIVO) Increases the accumulation of [3H]-DNM substantially, may reverse MDR by inhibiting the P-gp function Induces the anti-tumor activity of doxorubicin by inhibiting the migratory ability of TNBC cells Potentiates the growth-inhibitory activity of Adriamycin (ADR) on MCF-7 ADR-resistant human breast cancer cells Up-regulates Bcl-2 expression through OR transactivation in MCF-7 cells Reverses cisplatin resistance in triple-negative MDA-MB-468 breast cancer cells via inhibition of cytochrome P450 1B1 enzyme Induces cell-cycle arrest in MDA-MB-231 and BT474 cells through downregulation of Skp2 protein, induces p27 expression in MDA-MB-231 cells Decreases the expression of CDK6 in MC7 cells and AK549 cells Suppresses the expression of CyclinD1, p21, Twist and phospho p38MAPK, increases cell death by up regulating INXS and down regulating UCA1 lncRNAs in MCF-7 cells Down-regulates HSP70 expression, up-regulates GRP78 expression in Breast cancer cells Inhibits the enhanced VEGF secretion and Pin1 expression, decreases nuclear levels of c-Jun and HIF-1α in TAMR-MCF-7 cells Decreases the glucose uptake capacity of breast cancer cells by down-regulating the protein expression of GLUT1 Increases PTEN and decreases lipid peroxides in PBMCs levels Inhibits COX-2-mediated angiogenesis in human endothelial cells Reduces the expression of phospho-JAK1 and phospho-STAT3 and decreased STAT3-dependent luciferase reporter gene activity in the BT-474 cells Exhibits inhibitory effects on P-glycoprotein (P-gp) and CYP3A4 Decreases the expression of Wnt and GSK 3β in KBCHR8-5 cells and subsequently modulates P-gp overexpression Combined with resveratrol and catechin, Causes upregulation of FOXO1 (forkhead box O1) and NFKBIA (IkappaBalpha), thus activating apoptosis and potentially inhibiting NfkappaB (nuclear factor kappaB) activity. (IN VIVO, NUDE MICE created from green fluorescent protein-tagged MDA-MB-435 bone metastatic variant) Induces radio-sensitization through inhibiting the ATM kinase ( IN VIVO- DLD-1 human colorectal cancer xenograft model in nude mice, IN VITRO - DLD1, HeLa and MCF-7) Inhibits the binding of the transactivators CREB2, C-Jun, C/EBPβ and NF-κB and blocks the recruitment of the coactivator p300 to COX-2 promoter. (IN VIVO AND IN VITRO) Blocks estradiol stimulation of nuclear type II sites in the immature rat uterus, causing cell growth inhibition | |
| PubChem ID | 5280343 | |
| Additional PMIDs | 16462139 18655183 21400027 23661994 25968914 26941539 26748999 27224244 28280414 29076772 28462502 29491634 30810849 30948047 31982837 32612988 7923555 7674820 15182386 34611857 25298669 15905060 16968064 18954533 26922854 27198988 12769521 23569988 33625319 29434473 30306879 32097663 32159961 34268250 33134711 20447470 20803121 24060926 26491966 9449200 24573487 28822757 16596234 21042744 23664836 29905475 33728016 33682528 18655187 19617894 25940566 34431317 35178359 24959911 25446499 16619521 18024139 29844670 24019576 23000408 27143878 20798532 30599890 14980703 16777995 18958418 21857970 25278361 27392941 27175602 28121480 28752532 30025823 31602954 1879042 8509221 8162591 9367858 9381980 10601582 11052628 11562764 18032389 15937998 34254227 33341499 22119371 22447039 29185031 11597122 | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:578949-1 | |
| Safety | NA |