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Arsenic trioxide induces G2/M arrest in hepatocellular carcinoma cells by increasing the tumor suppressor PTEN expression.
MedLine Citation:
PMID:  22730174     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 24h 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. © 2012 Wiley Periodicals, Inc.
Authors:
Xinyu Zhang; Shuzhao Jia; Shumeng Yang; Yue Yang; Tuoyun Yang; Yanmei Yang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-21
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  -     ISSN:  1097-4644     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
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