Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma cell line U2-OS/MTX300 via mitochondrial dysfunction and dephosphorylation of Akt

Xianbiao Xie, Junqiang Yin, Qiang Jia, Jin Wang, Changye Zou, Kari J. Brewer, Chiara Colombo, Yaofei Wang, Gang Huang, Jingnan Shen

Research output: Contribution to journalArticlepeer-review

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 cytometry 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 dephosphorylation 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.

Original languageEnglish
Pages (from-to)687-693
Number of pages7
JournalOncology Reports
Volume26
Issue number3
DOIs
Publication statusPublished - Sep 2011

Keywords

  • Akt
  • Apoptosis
  • Methotrexate
  • Mito-chondria
  • Osteosarcoma
  • Quercetin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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