Sorafenib Induces Apoptosis in Hepatocellular Carcinoma Cells by Inhibiting c-Myc and Prothymosin-Alpha

Abstract

The anti-apoptotic protein prothymosin alpha (PTMA) is overexpressed in various cancers, including hepatocellular carcinoma (HCC). Earlier studies have shown that PTMA blocks apoptosis in cancer cells by inhibiting caspase-9 activation and apoptosome formation. Our recent study shows that silencing of PTMA potentiates the mitochondria-dependent apoptosis pathway in sorafenib-treated HCC cells, leading to Bax translocation, pBad dephosphorylation, and cytochrome c release. Our findings also indicate that the pERK/c-Myc/Max/PTMA axis represents a newly identified target of sorafenib in chemotherapy against HCC.