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

  • Authors:
    • Xianbiao Xie
    • Junqiang Yin
    • Qiang Jia
    • Jin Wang
    • Changye Zou
    • Kari J. Brewer
    • Chiara Colombo
    • Yaofei Wang
    • Gang Huang
    • Jingnan Shen
  • View Affiliations

  • Published online on: May 26, 2011     https://doi.org/10.3892/or.2011.1328
  • Pages: 687-693
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.

Related Articles

Journal Cover

September 2011
Volume 26 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Xie X, Yin J, Jia Q, Wang J, Zou C, Brewer KJ, Colombo C, Wang Y, Huang G, Shen J, Shen J, et al: Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma cell line U2-OS/MTX300 via mitochondrial dysfunction and dephosphorylation of Akt. Oncol Rep 26: 687-693, 2011.
APA
Xie, X., Yin, J., Jia, Q., Wang, J., Zou, C., Brewer, K.J. ... Shen, J. (2011). Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma cell line U2-OS/MTX300 via mitochondrial dysfunction and dephosphorylation of Akt. Oncology Reports, 26, 687-693. https://doi.org/10.3892/or.2011.1328
MLA
Xie, X., Yin, J., Jia, Q., Wang, J., Zou, C., Brewer, K. J., Colombo, C., Wang, Y., Huang , G., Shen, J."Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma cell line U2-OS/MTX300 via mitochondrial dysfunction and dephosphorylation of Akt". Oncology Reports 26.3 (2011): 687-693.
Chicago
Xie, X., Yin, J., Jia, Q., Wang, J., Zou, C., Brewer, K. J., Colombo, C., Wang, Y., Huang , G., Shen, J."Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma cell line U2-OS/MTX300 via mitochondrial dysfunction and dephosphorylation of Akt". Oncology Reports 26, no. 3 (2011): 687-693. https://doi.org/10.3892/or.2011.1328