[NNIspm, a polyamine derivative, induces cellular senescence of human hepatoma HepG2 cells and its molecular mechanism].
This study is to examine the effects of NNIspm-mediated cellular senescence of HepG2 cells and elucidate its potential molecular mechanism. Cellular senescence was detected with senescence-associated beta-galactosidase staining. Cell cycle distribution, intracellular fluorescence intensity and accumulation of intracellular reactive oxygen species (ROS) were detected by high content screening (HCS). Protein expression was detected by Western blotting. Polyamines content was analyzed by high performance liquid chromatography (HPLC). The results demonstrated that NNIspm significantly induced HepG2 cells senescence. This effect was due to the decrease of intracellular polyamines, the arrest at G0/G1 phase and an increase of ROS level. The molecular senescence marker p21 increased significantly after NNIspm treatment. In contrast, the protein expressions of Cyclin E and CDK2 were obvious down-regulation. The results indicated that cellular senescence induced by NNIspm was one of its antitumor mechanisms.
Institute of Chemical Biology, Henan University, Kaifeng 475004, China.
Song-Qiang
SQ
Xie
Ya-Hong
YH
Zhang
Hui-Fang
HF
Lu
A-Chun
AC
Shen
Qian
Q
Li
Jing-Hua
JH
Li
Jin
J
Zhao
Chao-Jie
CJ
Wang
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D016922:Cellular Senescence / Q000187:drug effects*; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D016193:G1 Phase; D056945:Hep G2 Cells; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000970:Antineoplastic Agents; C475820:CCNE1 protein, human; C493956:CDKN1A protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015513:Oncogene Proteins; D011073:Polyamines; D017382:Reactive Oxygen Species; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2