title: Reactive oxygen species generation is essential for cisplatin-induced accelerated senescence in hepatocellular carcinoma.
abstract: Accelerated senescence is important because this process is involved in tumor suppression and has been induced by many chemotherapeutic agents. The platinum-based chemotherapeutic agent cisplatin displays a wide range of antitumor activities. However, the molecular mechanism of cisplatin-induced accelerated senescence in hepatocellular carcinoma (HCC) remains unclear. In the present study, the growth inhibitory effect of cisplatin on HepG2 and SMMC-7721 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cellular senescence was then assessed by β-galactosidase assay. Senescence-related factors, including p53, p21, and p16, were evaluated by quantitative reverse transcription-polymerase chain reaction. Reactive oxygen species (ROS) was analyzed by flow cytometry. Our results revealed that cisplatin reduced the proliferation of HepG2 and SMMC-7721 cells in a dose- and time-dependent manner. Senescent phenotype observed in cisplatintreated hepatoma cells was dependent on p53 and p21 activation but not on p16 activation. Furthermore, cisplatininduced accelerated senescence depended on intracellular ROS generation. The ROS scavenger N-acetyl-L-cysteine also significantly suppressed the cisplatin-induced senescence of HepG2 and SMMC-7721 cells. In conclusion, our results revealed a functional link between intracellular ROS generation and cisplatin-induced accelerated senescence, and this link may be used as a potential target of HCC.
authors.affiliation: Department of Hepatobiliary Surgery, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Qu
authors.forename: Ting
authors.initials: T
authors.lastname: Lin
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Wang
authors.forename: Sinan
authors.initials: S
authors.lastname: Liu
authors.forename: Hulin
authors.initials: H
authors.lastname: Chang
authors.forename: Xinsen
authors.initials: X
authors.lastname: Xu
authors.forename: Fandi
authors.initials: F
authors.lastname: Meng
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Jichao
authors.initials: J
authors.lastname: Wei
authors.forename: Minghui
authors.initials: M
authors.lastname: Tai
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Dong
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005434:Flow Cytometry; D056945:Hep G2 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin
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