title: 3-Methyl pyruvate enhances radiosensitivity through increasing mitochondria-derived reactive oxygen species in tumor cell lines.
abstract: Considerable interest has recently been focused on the special characteristics of cancer metabolism, and several drugs designed to modulate cancer metabolism have been tested as potential anticancer agents. To date, however, very few studies have been conducted to investigate the combined effects of anticancer drugs and radiotherapy. In this study, to evaluate the role of mitochondria-derived reactive oxygen species (ROS) in the radiation-induced cell death of tumor cells, we have examined the effect of 3-methyl pyruvate (MP). MP is a membrane-permeable pyruvate derivative that is capable of activating mitochondrial energy metabolism in human lung carcinoma A549 cells and murine squamous carcinoma SCCVII cells. Pretreatment with MP significantly enhanced radiation-induced cell death in both cell lines, and also led to increases in the mitochondrial membrane potential, intracellular adenosine triphosphate content, and mitochondria-derived ROS production following the exposure of the cells to X-rays. In A549 cells, MP-induced radiosensitization was completely abolished by vitamin C. In contrast, it was partially abolished in SCCVII cells. These results therefore suggest that the treatment of the cells with MP induced radiosensitization via the production of excess mitochondria-derived ROS in tumor cells.
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Sapporo 060-0818, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Nishida
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yasui
authors.forename: Masaki
authors.initials: M
authors.lastname: Nagane
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamamori
authors.forename: Osamu
authors.initials: O
authors.lastname: Inanami
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008928:Mitochondria / Q000378:metabolism* / Q000528:radiation effects*; D011773:Pyruvates / Q000008:administration & dosage*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D011773:Pyruvates; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; C104813:methyl pyruvate
keywords: 3-methyl pyruvate; A549 cells; SCCVII cells; mitochondrial metabolism; radiosensitization; reactive oxygen species (ROS)