Dimethyl fumarate induces necroptosis in colon cancer cells through GSH depletion/ROS increase/MAPKs activation pathway

• DOI: 10.1111/bph.13184
• Publication Date: 2015-05-08T06:12:59Z
• Authors: Xin Xie; Yu Zhao; Chun‐Yan Ma; Xiao‐Ming Xu; Yan‐Qiu Zhang; Chen‐Guang Wang; Jing Jin; Xin Shen; Jin‐Lai Gao; Na Li; Zhi‐Jie Sun; De‐Li Dong
• Keywords: Viability assay; Dimethyl fumarate; MTT assay

Background and Purpose Dimethyl fumarate ( DMF ) is a newly approved drug for the treatment of relapsing forms multiple sclerosis relapsing‐remitting sclerosis. Here, we investigated effects its metabolites mono‐methylfumarate MMF methanol) on different gastrointestinal cancer cell lines underlying molecular mechanisms involved. Experimental Approach Cell viability was measured by MTT or CCK 8 assay. Protein expressions were Western blot analysis. LDH release, live‐ dead‐cell staining, intracellular GSH levels, mitochondrial membrane potential examined using commercial kits. Key Results but not induced necroptosis, as demonstrated pharmacological tool necrostatin‐1, transmission electron microscopy, HMGB 1 release in CT 26 cells. The ‐induced decrease cellular levels well increase reactive oxygen species ROS inhibited co‐treatment with N ‐acetylcysteine NAC activated JNK , p38 ERK MAPKs cells inhibitors partially reversed viability. p38, activation increased autophagy responses SGC ‐7901, HC T116, HT 29 cells, inhibition did prevent Conclusion Implications metabolite necroptosis colon through mechanism involving depletion an .