Parkin induces apoptotic cell death in TNF-α-treated cervical cancer cells
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Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-α)-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-α-induced cell death. TNF-α-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 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]
Abstract
Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-α)-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-α-induced cell death. TNF-α-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 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]
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