The small heat shock protein αB-Crystallin protects versus withaferin A-induced apoptosis and confers a more metastatic phenotype in cisplatin-resistant ovarian cancer cells.

Since a majority of ovarian tumors recur in a drug-resistant form leaving patients few treatment options, the goal of this study was to explore phenotypic and molecular characteristics of a cisplatin-resistant ovarian cancer cell line (OVCAR8R) as compared to its cisplatin-sensitive syngeneic counterpart (OVCAR8) and to explore the effectiveness of a novel chemotherapeutic, Withaferin A (WA). In addition to unique morphological characteristics, the small heat shock proteins (Hsps) αB-Crystallin (HspB5) and Hsp27 are constitutively expressed along with increased expression of vimentin in OVCAR8R cells, while OVCAR8 cells do not endogenously express these Hsps, supporting that Hsp overexpression may confer resistance to chemotherapy and promote more aggressive tumor types. WA increases apoptosis in a dose-dependent manner in OVCAR8 cells, while OVCAR8R cells remain more viable at comparable doses of WA coincident with the upregulation of αB-Crystallin.