Overexpression of Prdx6 and resistance to peroxide-induced death in Hepa1-6 cells: Prdx suppression increases apoptosis

Abstract

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.

Overexpression of Peroxiredoxin 6 Protects Neoplastic Cells against Apoptosis in Canine Haemangiosarcoma

“…Furthermore, visualization of nuclear fragmentation by DAPI staining revealed that the nuclear fragmentation in the siR-PRDX6 transfected groups of all HSA cell lines was significantly increased compared with that of the control siRNA-transfected group. Consistent with our findings, previous transient transfection of Hepa1e6 cells with PRDX6 siRNA was shown to lead to a marked reduction in its expression and an increase in peroxide-induced cytotoxicity mediated by apoptosis; these results suggested that PRDX6 upregulation might be a tumour-supportive adaptation in cancer (Walsh et al, 2009). …”

PRDX6 promotes tumor development via the JAK2/STAT3 pathway in a urethane-induced lung tumor model

“…PRDX6 is a bifunctional protein with both glutathione peroxidase and iPLA2 activities and is the only mammalian 1-Cys member of the PRDX superfamily [34]. In a recent study, the overexpression of PRDX6 attenuated cisplatin-induced apoptosis in human ovarian cancer cells [11], whereas the reduction of PRDX6 expression increased cell death in liver cancer cells [35]. Invasion-and metastasispromoting actions of PRDX6 have been found in lung cancer cells [10,36].…”

Bioinformatics Analysis of Proteomic Profiles During the Process of Anti-Thy1 Nephritis

“…For example, ACAT1 (21,22) and ECHS1 (23,24) may be involved in lipid metabolism, whereas ATP6V1A and ATP6V1B2 mediate Hϩ transport (25,26). PRDX3 (27,28) and PRDX6 (29,30) have antioxidant effects, regulating apoptosis and cell damage by way of DLD (31). SUCLG2, SUCLA2, and TPI1 (32) play a role in ATP and/or GTP metabolism.…”