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

Many malignant tumors become resistant to tumor necrosisfactor-alpha (TNF-α)-induced cell death during carcinogenesis.In the present study, we examined whether parkin acts as atumor suppressor in HeLa cells, a human cervical cancer cellline resistant to TNF-α-induced cell death. TNF-α-treatmentalone did not affect HeLa cell viability. However, expressionof parkin restored TNF-α-induced apoptosis in HeLa cells.Increased cell death was due to the activation of the apoptoticpathway. Expression of parkin in TNF-α-treated HeLa cellsstimulated 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 thecaspase inhibitory protein, survivin. These results suggest thatparkin acts as a tumor suppressor in human cervical cancercells by modulating survivin expression and caspase activity.We propose that this pathway is a novel molecular mechanismby which parkin functions as a tumor suppressor.