Involvement of hydrogen peroxide production in erbstatin-induced apoptosis in human small cell lung carcinoma cells.
Tyrosine kinase inhibitor, erbstatin, induced morphological apoptosis and DNA fragmentation in human small cell lung carcinoma (SCLC) cells. Erbstatin-induced apoptosis was inhibited by antioxidants, whereas erbstatin-inhibited tyrosine phosphorylation was not affected by them. Erbstatin was shown by means of flow cytometry to induce hydrogen peroxide generation. Furthermore, hydrogen peroxide induced morphological apoptosis and DNA fragmentation in the SCLC cells. We also demonstrated that erbstatin-induced hydrogen peroxide production and DNA fragmentation were partially suppressed by inhibition of protein synthesis. Thus, erbstatin-induced apoptosis would be due to hydrogen peroxide generation via newly synthesized protein.
Simizu
S
S
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Imoto
M
M
Masuda
N
N
Takada
M
M
Umezawa
K
K
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology*; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity*; D006873:Hydroquinones / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D003513:Cycloheximide; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases; C048212:erbstatin