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 er bstatin-inhibited tyrosine phosphorylation was not affected by them. E rbstatin was shown by means of flow cytometry to induce hydrogen perox ide generation. Furthermore, hydrogen peroxide. induced morphological apoptosis and DNA fragmentation in the SCLC cells. We also demonstrate d that erbstatin-induced hydrogen peroxide production and DNA fragment ation were partially suppressed by inhibition of protein synthesis. Th us, erbstatin-induced apoptosis would be due to hydrogen peroxide gene ration via newly synthesized protein.