title: 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.
authors.affiliation: a School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group , College of Natural Sciences, Kyungpook National University , Taegu , Republic of Korea.
authors.forename: Hyeong Jun
authors.initials: HJ
authors.lastname: Ku
authors.affiliation: a School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group , College of Natural Sciences, Kyungpook National University , Taegu , Republic of Korea.
authors.forename: Oh-Shin
authors.initials: OS
authors.lastname: Kwon
authors.affiliation: a School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group , College of Natural Sciences, Kyungpook National University , Taegu , Republic of Korea.
authors.forename: Boem Sik
authors.initials: BS
authors.lastname: Kang
authors.affiliation: a School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group , College of Natural Sciences, Kyungpook National University , Taegu , Republic of Korea.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Lee
authors.affiliation: a School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group , College of Natural Sciences, Kyungpook National University , Taegu , Republic of Korea.
authors.forename: Hyun-Shik
authors.initials: HS
authors.lastname: Lee
authors.affiliation: a School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group , College of Natural Sciences, Kyungpook National University , Taegu , Republic of Korea.
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D004642:Emodin / Q000009:adverse effects*; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000209:etiology*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species
chemical_list: D017382:Reactive Oxygen Species; D007521:Isocitrate Dehydrogenase; D004642:Emodin
keywords: Antioxidant enzyme; antisense; apoptosis; emodin; redox status