Apoptotic and necrotic action mechanisms of trimethyltin in human hepatoma G2 (HepG2) cells.
In evaluating the cytotoxic effects and the mechanisms of the apoptotic and necrotic actions of trimethyltin chloride (TMT) on human hepatoma G2 (HepG2) cells, the present study focused on the involvement of antiproliferation, DNA damage, cell death, apoptosis-related proteins, and p53-dependent transcriptional activity. Twenty-four hour TMT treatments (4-64 microM) induced apoptosis and necrosis in HepG2 cells. Thirty-two micromolar and higher concentration significantly increases cell death. DNA damage was observed at 8 microM. Additionally, TMT increased the activity of cellular caspase-3 and the release of mitochondrial cytochrome c in a concentration-dependent manner. Our data demonstrated that the Bcl-2 family of proteins was involved in the apoptotic process but that p53 expression level was not affected. The results of luciferase reporter assay indicated that TMT-induced apoptosis seemed to adopt a transcription-dependent route, by activating p53 target genes such as PUMA and p21.
Cai
Jiali
J
Key Laboratory of the Ministry of Education for Coast and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen 361005, China.
Wang
Mengmeng
M
Li
Bowen
B
Wang
Chonggang
C
Chen
Yixin
Y
Zuo
Zhenghong
Z
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D020552:Comet Assay; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D009336:Necrosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014298:Trimethyltin Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014298:Trimethyltin Compounds; D016159:Tumor Suppressor Protein p53; D045304:Cytochromes c; C040533:trimethyltin chloride; D053148:Caspase 3