Methyl methanesulfonate induces necroptosis in human lung adenoma A549 cells through the PIG-3-reactive oxygen species pathway

• DOI: 10.1007/s13277-015-3531-y
• Publication Date: 2015-10-15T18:47:11Z
• Authors: Ying Jiang; Shigang Shan; Linfeng Chi; Guanglin Zhang; Xiangjing Gao; Hongjuan Li; Xinqiang Zhu; Jun Yang
• Keywords: Adenoma; 0303 health sciences; Lung Neoplasms; Dose-Response Relationship, Drug; Cell Survival; Blotting, Western; Intracellular Signaling Peptides and Proteins; Apoptosis; Methyl Methanesulfonate; Necrosis; 03 medical and health sciences; A549 Cells; Proto-Oncogene Proteins; Humans; RNA Interference; Reactive Oxygen Species; Antineoplastic Agents, Alkylating; DNA Damage; Signal Transduction

Methyl methanesulfonate (MMS) is an alkylating agent that can induce cell death through apoptosis and necroptosis. The molecular mechanisms underlying MMS-induced have been studied extensively; however, little known about the mechanism for Therefore, we first established necroptosis model using human lung carcinoma A549 cells. It was found that, within a 24-h period, although MMS at concentrations of 50, 100, 200, 400, 800 μM DNA damage, only higher (400 μM) treatment lead to in cells, as it could be inhibited by specific necroptotic inhibitor necrostatin-1, but not apoptotic carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-fmk). further confirmed induction biomarkers including depletion cellular NADH ATP leakage LDH. This also concurrent with increased expression p53, p53-induced gene 3 (PIG-3), high mobility group box-1 protein (HMGB1), receptor interaction kinase (RIP) apoptosis-associated caspase-3 caspase-9 proteins. Elevated reactive oxygen species (ROS) level involved this process ROS (4-amino-2,4-pyrrolidine-dicarboxylic acid (APDC)) inhibit death. Interestingly, knockdown PIG-3 small interfering RNA (siRNA) generation ROS. Taken together, these results suggest probably PIG-3-ROS pathway.