Arsenic trioxide induces G2/M arrest in hepatocellular carcinoma cells by increasing the tumor suppressor PTEN expression | Zendy

Zhang Xinyu | Zendy; Jia Shuzhao | Zendy; Yang Shumeng | Zendy; Yang Yue | Zendy; Yang Tuoyun | Zendy; Yang Yanmei | Zendy

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Arsenic trioxide induces G2/M arrest in hepatocellular carcinoma cells by increasing the tumor suppressor PTEN expression

Author(s) -

Zhang Xinyu,

Jia Shuzhao,

Yang Shumeng,

Yang Yue,

Yang Tuoyun,

Yang Yanmei

Publication year - 2012

Publication title -

journal of cellular biochemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.028

H-Index - 165

eISSN - 1097-4644

pISSN - 0730-2312

DOI - 10.1002/jcb.24230

Subject(s) - arsenic trioxide , pten , wee1 , cyclin dependent kinase 1 , cell cycle checkpoint , cancer research , downregulation and upregulation , cell cycle , chemistry , cyclin b1 , protein kinase b , cell culture , viability assay , cdc25 , cell , biology , phosphorylation , signal transduction , pi3k/akt/mtor pathway , apoptosis , biochemistry , genetics , gene

Arsenic trioxide (As 2 O 3 ), an effective agent against acute promyelocytic leukemia, has been reported to inhibit the viability of solid tumors cell lines recently. The detailed molecular mechanism underlying the As 2 O 3 ‐induced inactivation of the cdc2 and possible functional role of PTEN in the observed G2/M arrest has yet to be elucidated. Here, we assessed the role of PTEN in regulation of As 2 O 3 ‐mediated G2/M cell cycle arrest in Hepatocellular carcinoma cell lines (HepG2 and SMMC7721). After 24 h following treatment, As 2 O 3 induced a concentration‐dependent accumulation of cells in the G2/M phase of the cell cycle. The sustained G2/M arrest by As 2 O 3 is associated with decreased cdc2 protein and increased phospho‐cdc2(Tyr15). As 2 O 3 treatment increased Wee1 levels and decreased phospho‐Wee1(642). Moreover, As 2 O 3 substantially decreased the Ser473 and Thr308 phosphorylation of Akt and upregulated PTEN expression. Downregulation of PTEN by siRNA in As 2 O 3 ‐treated cells increased phospho‐Wee1(Ser642) while decreased phospho‐cdc2(Tyr15), resulting in decreased the G2/M cell cycle arrest. Therefore, induction of G2/M cell cycle arrest by As 2 O 3 involved upregulation of PTEN. J. Cell. Biochem. 113: 3528–3535, 2012. © 2012 Wiley Periodicals, Inc.

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