Overexpression of Prdx6 and Resistance to Peroxide-Induced Death in Hepa1-6 Cells: Prdx6 Suppression Increases Apoptosis
Peroxiredoxins are thiol-specific antioxidants that catalyze the reduction of cellular peroxides and protect cells from ROS-mediated damage and death. Peroxiredoxin gene expression is up-regulated in a number of cancers, suggesting a possible role in cancer cell maintenance. Prdx6, a cytoplasmic protein elevated in certain cancers, is highly expressed in liver and transcriptionally regulated by various oxidative stresses. In the present study, we found that the cancerous Hepa1-6 hepatoma cell line is significantly more resistant to peroxide-induced cytotoxicity than the non-cancerous H2.35 cell line. We also demonstrated that Hepa1-6 cells express approximately 3-fold more Prdx6 mRNA and 2.5-fold more Prdx6 protein than H2.35 cells. Treatment with mithramycin A resulted in a nearly 20% reduction in Prdx6 mRNA in Hepa1-6 cells, suggesting a possible role for Sp1 in Prdx6 up-regulation. We hypothesized that suppression of Prdx6 in Hepa1-6 cells would increase susceptibility to peroxide-induced cell death. Transient transfection of Hepa1-6 cells with Prdx6 siRNA led to a marked reduction in Prdx6 expression, and an increase in peroxide-induced cytotoxicity by apoptosis. Together, these data demonstrate an important anti-apoptotic function for Prdx6 in cancerous liver cells, and suggest that its up-regulation may be a tumor-supportive adaptation in cancerous states.
Walsh, B.; Pearl, A.; Suchy, S.; Tartaglio, J.; Visco, K.; and Phelan, Shelley A., "Overexpression of Prdx6 and Resistance to Peroxide-Induced Death in Hepa1-6 Cells: Prdx6 Suppression Increases Apoptosis" (2009). Biology Faculty Publications. 16.
*Walsh B, *Pearl A, *Suchy S, *Tartaglio J, *Visco K, & Phelan SA. (2009) Overexpression of Prdx6 and Resistance to Peroxide-Induced Death in Hepa1-6 Cells: Prdx6 Suppression Increases Apoptosis. Redox Report 14(6):275-284. *denotes student author