c-Myc degradation induced by DNA damage results in apoptosis of CHO cells.
Although tripchlorolide (TC), a compound purified from a Chinese herb Tripterygium Wilfordii Hook, has been demonstrated to be a potent antitumor agent, its mechanisms of action are unknown. The present study shows that TC induces apoptosis of Chinese Hamster Ovary (CHO) cells. Most strikingly, TC was particularly potent in inducing apoptosis of the UV41 mutant CHO cells, which are deficient in the ERCC4 gene encoding a nucleotide excision repair protein. TC caused a higher level of DNA damage in UV41 cells than those in the wild-type CHO cells or EM9 cells, which are deficient in single-strand break repair. These results provided a critical link between apoptotic hypersensitivity and DNA damage in defective nucleotide excision repair pathway of UV41 cells by TC treatment. Further analysis showed that degradation of the c-Myc protein in TC-treated UV41 cells was much stronger than those in the wild-type CHOAA8 and the EM9. A proteasome inhibitor, MG132, reduced both the degradation of c-Myc and apoptosis in TC-treated UV41 cells. Expression of exogenous c-Myc also inhibited apoptosis of TC-treated UV41 cells. These results indicate that c-Myc degradation induced by DNA damage in the presence of TC contributes to induction of apoptosis of UV41 cells.
Jiang
Man-Rong
MR
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
Li
Yuan-Chao
YC
Yang
Ying
Y
Wu
Jia-Rui
JR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D016466:CHO Cells; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004249:DNA Damage; D004224:Diterpenes / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000378:metabolism; D010616:Phenanthrenes; D046988:Proteasome Endopeptidase Complex; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
D000970:Antineoplastic Agents; D004224:Diterpenes; D009097:Multienzyme Complexes; D010616:Phenanthrenes; D016271:Proto-Oncogene Proteins c-myc; D025801:Ubiquitin; C068051:tripchlorolide; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex