标题：Novel copper complex CTB regulates methionine cycle induced TERT hypomethylation to promote HCC cells senescence via mitochondrial SLC25A26
作者：Jin C.; Li Y.; Su Y.; Guo Z.; Wang X.; Wang S.; Zhang F.; Zhang Z.;等 更多 作者机构：[Jin, C] Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210 更多
通讯作者地址：[Shao, J] Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Jiangsu Key 更多
来源：Cell Death and Disease
摘要：Related research has recognized the vital role of methionine cycle metabolism in cancers. However, the role and mechanism of methionine cycle metabolism in hepatocellular carcinoma are still unknown. In this study, we found that [Cu(ttpy-tpp)Br2]Br (Referred to as CTB) could induce hepatocellular carcinoma cells senescence, which is a new copper complex synthesized by our research group. Interestingly, CTB induces senescence by inhibiting the methionine cycle metabolism of HCC cells. Furthermore, the inhibitory effect of CTB on the methionine cycle depends on mitochondrial carrier protein SLC25A26, which was also required for CTB-induced HCC cells senescence. Importantly, we found that CTB-induced upregulation of SLC25A26 could cause abnormal methylation of TERT and inhibited TERT expression, which is considered to be an essential cause of cell senescence. The same results were also obtained in vivo, CTB inhibits the growth of subcutaneously implanted tumors in nude mice and promoted the expression of senescence markers in tumor tissues, and interference with SLC25A26 partially offset the antitumor effect of CTB. © 2020, The Author(s).