title: Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma cell line U2-OS/MTX300 via mitochondrial dysfunction and dephosphorylation of Akt.
abstract: Quercetin is the most abundant polyphenolic flavonoid found in plants. Several studies suggest that it has potent anticancer effects. The present study examines the apoptosis-inducing activity and the underlying mechanism of action of quercetin in a methotrexate (MTX)-resistant osteosarcoma model. Our results showed that quercetin inhibited cell viability in a dose-dependent manner and there was no cross-resistance between MTX and quercetin in U2-OS/MTX300 cells. The induction of apoptosis was observed by flow cyto-metry and fluorescence staining experiments. Quercetin-induced apoptosis was accompanied by a significant reduction of mitochondrial membrane potential, release of mitochondrial cytochrome c to the cytosol, activation of caspase-3, down-regulation of Bcl-2, p-Bad and up-regulation of Bax. A remarkable dephospho-rylation of Akt was also detected after quercetin treatment. Furthermore, transduction with constitutively active Akt protected against the quercetin-induced dephosphorylation of Akt and Bad as well as poly(ADP-ribose)polymerase (PARP) degradation, while combined treatment with quercetin and LY294002 enhanced the dephosphorylation of Akt, Bad and PARP cleavage in U2-OS/MTX300 cells. Taken together, our results demonstrate that quercetin-induced apoptosis in the MTX-resistant osteosarcoma cells U2-OS/MTX300 was mediated via mitochondrial dysfunction and dephosphorylation of Akt.
authors: Department of Orthopaedic Oncology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, PR China.
authors: Xianbiao
authors: X
authors: Xie
authors: Junqiang
authors: J
authors: Yin
authors: Qiang
authors: Q
authors: Jia
authors: Jin
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authors: Wang
authors: Changye
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authors: Zou
authors: Kari J
authors: KJ
authors: Brewer
authors: Chiara
authors: C
authors: Colombo
authors: Yaofei
authors: Y
authors: Wang
authors: Gang
authors: G
authors: Huang
authors: Jingnan
authors: J
authors: Shen