Parkin induces apoptotic cell death in TNF-α-treated cervical cancer cells

Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-alpha)-induced cell death during carcinogenesis. In the present study, we examined whether parkin acts as a tumor suppressor in Hela cells, a human cervical cancer cell line resistant to TNF-alpha-induced cell death. TNF-alpha-treatment alone did not affect HeLa cell viability. However, expression of parkin restored TNF-alpha-induced apoptosis in HeLa cells. Increased cell death was due to the activation of the apoptotic pathway. Expression of parkin in TNF-alpha-treated HeLa cells stimulated cleavage of the pro-apoptotic proteins caspase-8, -9, -3, -7 and poly ADP ribose polymerase (PARP). In addition, parkin expression resulted in decreased expression of the caspase inhibitory protein, survivin. These results suggest that parkin acts as a tumor suppressor in human cervical cancer cells by modulating survivin expression and caspase activity. We propose that this pathway is a novel molecular mechanism by which parkin functions as a tumor suppressor. [BMB Reports 2012; 45(9): 526-531]