Cancer: Leukemia, prostate
Action: MDR, apoptosis-inducing
Quercetin is a plant-derived flavonol found in many fruits, vegetables, leaves and grains. It is also found in red wine.
MDR/ Apoptotic-inducing
Natural products from plants such as flavonoids are potential drugs to overcome multi-drug resistance (MDR) in cancer treatments. Quercetin exhibits cytotoxicity against erythroleukemic cells: IC50 are 11.0 +/- 2.0 micromol/L and 5.0 +/- 0.4 micromol/L for K562 and K562/adr, respectively. Quercetin induces cell death via apoptosis in both K562 and K562/adr cells and does not inhibit Pgp-mediated efflux of 99mTc-MIBI. Quercetin (10 micromol/L, 3 h) and etoposide (100 micromol/L, 24 hours) induce similar levels of apoptosis in K562 and K562/adr cells.
Quercetin induces an increase followed by a decrease in inner mitochondrial membrane potential |DeltaPsim| value depending on its concentration. A decrease in the |DeltaPsim| value is associated with an increase in the percentage of early apoptotic cells.
It is clearly shown that quercetin results in a spontaneous DeltaPsim change during apoptotic induction. Therefore, quercetin is potentially an apoptotic-inducing agent, which reacts at the mitochondrial level (Kothan et al., 2004).
MDR
Expression of the MDR1 gene, which encodes P-glycoprotein, is increased under some stress conditions. It has been reported that quercetin, a bioflavonoid, inhibits the expression of heat-shock proteins. The effects of quercetin have been identified on the MDR1 gene expression in the human hepatocarcinoma cells line, HepG2. The increase of P-glycoprotein synthesis and MDR1 mRNA accumulation caused by exposure to arsenite were inhibited by quercetin. Although many drugs that prevent the P-glycoprotein function have been reported, this is the first report to describe the inhibition of MDR1 expression by a reagent (Kioka et al., 1992).
Leukemia
Leukemia cells were treated with quercetin, after which apoptosis, Mcl-1 expression, and Bax activation and translocation were evaluated. Quercetin-induced apoptosis was accompanied by Mcl-1 down-regulation and Bax conformational change and mitochondrial translocation that triggered cytochrome c release. In vivo administration of quercetin attenuated tumor growth in U937 xenografts. The TUNEL-positive apoptotic cells in tumor sections increased in quercetin-treated mice as compared with controls.
These data suggest that quercetin may be useful for the treatment of leukemia by preferentially inducing apoptosis in leukemia versus normal hematopoietic cells through a process involving Mcl-1 down-regulation, which, in turn, potentiates Bax activation and mitochondrial translocation, culminating in apoptosis (Cheng et al., 2010).
Prostate Cancer
The anti-angiogenic activity of quercetin was probed using ex vivo, in vivo and in vitro models. Angiogenesis is a crucial step in the growth and metastasis of cancers, since it enables the growing tumor to receive oxygen and nutrients. Quercetin (20 mg/kg/d) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model, indicating that quercetin inhibited tumorigenesis by targeting angiogenesis.
Furthermore, quercetin reduced the cell viability and induced apoptosis in prostate cancer cells, which were correlated with the down-regulation of AKT, mTOR and P70S6K expressions. Collectively, these results suggest that quercetin inhibits tumor growth and angiogenesis by targeting VEGF-R2 regulated AKT/mTOR/P70S6K signaling pathway, and could be used as a potential drug candidate for cancer therapy (Pratheeshkumar et al., 2012).
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