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

BMB Rep. 2012; 45(9): 526-531

Kyunghong Lee#, Min Ho Lee#, Yeo Wool Kang, Ki-Jong Rhee, Tae Ue Kim & Yoon Suk Kim*

Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 220-710, Korea

Correspondence to: Tel: +82-33-760-2860; Fax: +82-33-760-5224; E-mail: yoonsukkim@yonsei.ac.kr

Received: May 11, 2012; Revised: May 30, 2012; Accepted: June 4, 2012; Published online: September 30, 2012.

ABSTRACT: Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-α)-induced celldeath 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 theapoptotic 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.; Keywords: Apoptosis, Caspase, Cervical cancer, Parkin, TNF-α

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