Nuclear proteome analysis of cisplatin-treated HeLa cells.
Cisplatin has been widely accepted as one of the most efficient anticancer drugs for decades. However, the mechanisms for the cytotoxic effects of cisplatin are still not fully understood. Cisplatin primarily targets DNA, resulting in the formation of DNA double strand breaks and eventually causing cell death. In this study, we applied two-dimensional electrophoresis coupled with LC-MS/MS to analyze the nuclear proteome of HeLa cells treated with cisplatin, in an effort to uncover new mechanistic clues regarding the cellular response to cisplatin. A total of 19 proteins were successfully identified, and these proteins are involved in a variety of basal metabolic and biological processes in cells, including biosynthesis, cell cycle, glycolysis and apoptosis. Six were related to the regulation of mRNA splicing, and we therefore asked whether the Fas gene might undergo alternative splicing following cisplatin treatment. This proved to be the case, as the splicing forms of Fas were modified in cisplatin-treated HeLa cells. This work provides novel information, from the perspective of the nuclear response, for understanding the cytotoxicity caused by cisplatin-induced DNA damage.
Wu
Wei
W
Department of Toxicology, Zhejiang University School of Public Health, and Department of Pharmacy, Lishui People's Hospital, Zhejiang 310058, China.
Yan
Chunlan
C
Gan
Tieer
T
Chen
Zhanghui
Z
Lu
Xianghong
X
Duerksen-Hughes
Penelope J
PJ
Zhu
Xinqiang
X
Yang
Jun
J
D017398:Alternative Splicing / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000187:drug effects*; D020543:Proteome / Q000187:drug effects* / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics
D000970:Antineoplastic Agents; C491901:FAS protein, human; D009687:Nuclear Proteins; D020543:Proteome; D019014:fas Receptor; D002945:Cisplatin