p14ARF sensitizes human osteosarcoma cells to cisplatin-induced apoptosis in a p53-independent manner

Xiang Wei Yuan, Xiao-Feng Zhu, Xiu Fang Huang, Pu Yi Sheng, Ai Shan He, Zi Bo Yang, Rong Deng, Gong Kan Feng, Wei Ming Liao

    Research output: Contribution to journalArticle

    5 Scopus citations

    Abstract

    The tumor suppressor p14ARF, encoded by the INK4a/ARF locus, is often disrupted in human cancers. p14ARF triggers cell cycle arrest and sensitizes cells to apoptosis in the presence of collateral signals. To investigate the role of p14ARF in chemotherapeutic drugs-induced apoptosis, p14ARF was overexpressed by stable transfection in human osteosarcoma cell lines, U2OS (p53-wt/p14ARF-null) and MG63 (p53-mt/p14ARF-null). The results showed that ectopic p14ARF sensitized both cell lines to cisplatin-induced cytotoxicity and apoptosis. This sensitization of cisplatin-induced apoptosis was associated with upregulation of p53, Bax and p21 in U2OS cells. Conversely, such a result was not observed in MG63 cells. Moreover, the sensitization of cisplatin-induced cytotoxicity in U2OS cells was unaltered by p53 siRNA. Together, we show here p14ARF sensitizes human osteosarcoma cells to cisplatin-induced apoptosis in a p53-independent manner. Proper combinations of p14ARF gene transfer and conventional chemotherapy may be a valuable strategy in human osteosarcoma treatment.

    Original languageEnglish (US)
    Pages (from-to)1074-1080
    Number of pages7
    JournalCancer Biology and Therapy
    Volume6
    Issue number7
    DOIs
    StatePublished - Jan 1 2007

    Keywords

    • Apoptosis
    • Cisplatin
    • Osteosarcoma
    • p14ARF
    • p53

    ASJC Scopus subject areas

    • Molecular Medicine
    • Oncology
    • Pharmacology
    • Cancer Research

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  • Cite this

    Yuan, X. W., Zhu, X-F., Huang, X. F., Sheng, P. Y., He, A. S., Yang, Z. B., Deng, R., Feng, G. K., & Liao, W. M. (2007). p14ARF sensitizes human osteosarcoma cells to cisplatin-induced apoptosis in a p53-independent manner. Cancer Biology and Therapy, 6(7), 1074-1080. https://doi.org/10.4161/cbt.6.7.4324