Gallic acid induces G2/M phase cell cycle arrest via regulating 14-3-3β release from Cdc25C and Chk2 activation in human bladder transitional carcinoma cells.

Abstract

SCOPE:

Cell cycle regulation is a critical issue in cancer treatment. Previously, gallic acid (GA) has been reported to possess anticancer ability. Here, we have evaluated the molecular mechanism of GA on cell cycle modulation in a human bladder transitional carcinoma cell line (TSGH-8301 cell).

METHODS AND RESULTS:

Using flow cytometer analysis, exposure of the cells to 40 μM GA resulted in a statistically significant increase in G2/M phase cells, which was accompanied by a decrease in G0/G1 phase cells. GA-treated cells resulted in significant growth inhibition in a dose-dependent manner accompanied by a decrease in cyclin-dependent kinases (Cdk1), Cyclin B1, and Cdc25C, but significant increases in p-cdc2 (Tyr-15) and Cip1/p21 by western blotting. Additional mechanistic studies showed that GA induces phosphorylation of Cdc25C at Ser-216. This mechanism leads to its translocation from the nucleus to the cytoplasm resulting in an increased binding with 14-3-3β. When treated with GA, phosphorylated Cdc25C can be activated by ataxia telangiectasia-mutated checkpoint kinase 2 (Chk2). This might be a DNA damage response as indicated by Ser-139 phosphorylation of histine H2A.X. Furthermore, treatment of the cells with a Chk2 inhibitor significantly attenuated GA-induced G2/M phase arrest.

CONCLUSION:

These results indicate that GA can induce cell cycle arrest at G2/M phase via Chk2-mediated phosphorylation of Cdc25C in a bladder transitional carcinoma cell line.

• Authors: Ting-Tsz Ou, Chau-Jong Wang, Yung-Shu Lee, Cheng-Hsun Wu, Huei-Jane Lee
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 54 Issue 12 Pg. 1781-90 (Dec 2010) ISSN: 1613-4133 [Electronic] Germany
• PMID: 20564478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• 14-3-3 Proteins
• Cyclin B1
• Gallic Acid
• Checkpoint Kinase 2
• CHEK2 protein, human
• Protein Serine-Threonine Kinases
• Cyclin-Dependent Kinases
• CDC25C protein, human
• cdc25 Phosphatases

Topics

• 14-3-3 Proteins (metabolism)
• Analysis of Variance
• Cell Cycle
• Cell Division
• Cell Line, Tumor
• Checkpoint Kinase 2
• Cyclin B1 (metabolism)
• Cyclin-Dependent Kinases (metabolism)
• G2 Phase
• Gallic Acid (pharmacology)
• Humans
• Phosphorylation
• Protein Serine-Threonine Kinases (metabolism)
• Urinary Bladder Neoplasms (metabolism)
• cdc25 Phosphatases (metabolism)