Proapoptotic protein Smac mediates apoptosis in cisplatin-resistant ovarian cancer cells when treated with the anti-tumor agent AT101.

ABSTRACT: Chemoresistance of ovarian cancer has been previously attributed to the expression and activation of Bcl-2 family proteins. BH3-mimetic molecules possessing potential anticancer activity are able to inhibit antiapoptotic Bcl-2 family proteins. AT101 (R-(-)-gossypol), a natural BH3-mimetic molecule, has shown anti-tumor activity as a single agent and in combination with standard anticancer therapies in a variety of tumor models. Here, we report the effect of AT101 on apoptosis in cisplatin-resistant ovarian cancer cells and identify the major molecular events that determine sensitivity. AT101 induced cell apoptosis by activating Bax through a conformational change, translocation, and oligomerization. The inhibition of Bax expression only partially prevented caspase-3 cleavage. However, the

SUBMITTER: Hu W 

PROVIDER: S-EPMC3249122 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature