GADD45α mediates arsenite-induced cell apoptotic effect in human hepatoma cells via JNKs/AP-1-dependent pathway

✍ Scribed by Ming Gao; Wen Dong; Meiru Hu; Ming Yu; Liang Guo; Lu Qian; Ning Guo; Lun Song

• Book ID: 102876113
• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 569 KB
• Volume: 109
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.22509

✦ Synopsis

Abstract

Arsenite (As(III)), an effective chemotherapeutic agent for the acute promyelocytic leukemia (APL) and multiple myeloma (MM), might be also a promise for the therapy of other cancers, including the solid tumors. However, the molecular bases of arsenite‐induced cytotoxicity in the tumor cells have not been fully defined. In this study, we have disclosed that arsenite effectively induces the apoptotic response in the HepG2 human hepatoma cells by triggering GADD45α induction and the subsequent activation of JNKs/AP‐1 cell death pathway. However, signaling events relating to GADD45α/JNKs/AP‐1 pathway activation have not been observed in HL7702 human diploid hepatic cells under the same arsenite exposure condition. Our results thus have illustrated the selective pro‐apoptotic role of arsenite in the hepatoma cells by activating GADD45α‐dependent cell death pathway whereas with little effect on the normal hepatic cells. The approaches to up‐regulate GADD45α levels might be helpful in improving the chemotherapeutic action of arsenite on certain solid tumors including hepatoma. J. Cell. Biochem. 109: 1264–1273, 2010. © 2010 Wiley‐Liss, Inc.