IDH2 knockdown sensitizes tumor cells to emodin cytotoxicity in vitro and in vivo

Abstract

Although reactive oxygen species (ROS) work as second messengers at sublethal concentrations, higher levels of ROS can kill cancer cells. Since cellular ROS levels are determined by a balance between ROS generation and removal, the combination of ROS generators, and the depletion of reducing substances greatly enhance ROS levels. Emodin (1,3,8-trihydroxy-6-methyl anthraquinone), a natural anthraquinone derivative from the root and rhizome of numerous plants, is a ROS generator that induces apoptosis in cancer cells. The major enzyme to generate mitochondrial NADPH is the mitochondrial isoenzyme of NADP⁺-dependent isocitrate dehydrogenase (IDH2). In this report, we demonstrate that IDH2 knockdown effectively enhances emodin-induced apoptosis of mouse melanoma B16F10 cells through the regulation of ROS generation. Our findings suggest that suppression of IDH2 activity results in perturbation of the cellular redox balance and, ultimately, exacerbate emodin-induced apoptotic cell death in B16F10 cells. Our results strongly support a therapeutic strategy in the management of cancer that alters the intracellular redox status by the combination of a ROS generator and the suppression of antioxidant enzyme activity.

Keywords:

• Antioxidant enzyme
• antisense
• apoptosis
• emodin
• redox status

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding information

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (Grant No. NRF-2015R1A4A1042271).