Parkin induces apoptotic cell death in TNF-αtreated cervical cancer cells

Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-α)-induced celldeathduring carcinogenesis. In the present study, we examined whether parkin acts as a tumor suppressor inHeLa cells, a human cervical cancer cell line resistant to TNF-α-induced cell death. TNF-a-treatment alone did not affect HeLa cell viability. However, expression of parkin restored TNF-α-induced apoptosis in HeLa cells. Increased cell death was due to the activation of the apoptotic pathway. Expression of parkin in TNF-α-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 atumor 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 parkinfunctions as a tumor suppressor.