Silencing of mitochondrial NADP⁺-dependent isocitrate dehydrogenase gene enhances selenite-induced apoptosis

Abstract

Selenium has been shown to play a chemopreventive role in human cancer, presumably by inducing tumour cell apoptosis. Selenite is thought to induce oxidative stress by the generation of the superoxide anion and catalysing the oxidation of thiol groups. It has previously been reported that control of the mitochondrial redox balance is a primary function of mitochon-drial NADP⁺-dependent isocitrate dehydrogenase (IDPm) by supplying NADPH for antioxidant systems. When investigating whether IDPm would be a vulnerable target of selenite, the loss of enzyme activity was observed. Transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly decreased activity of IDPm and enhanced cells’ susceptibility of selenite-induced apoptosis, as indicated by morphological evidence of apoptosis, DNA fragmentation and the modulation of mitochondrial function and apoptotic marker proteins. These results suggest that IDPm siRNA sensitizes HeLa cells to selenite-induced apoptotic cell death, presumably through the perturbation of the cellular redox status.

Keywords::

• Selenite
• antioxidant enzyme
• siRNA
• redox status

Declaration of interest: This work was supported by National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (0720250) and National Research Foundation of Korea Grant funded by the Korean Government (2009-0093187). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This paper was first published online on Early Online on 31 December 2009.