Erbstatin, a tyrosine kinase inhibitor, has antitumor activity on L1210 mouse leukemia. We tried to find the mechanism of this cytotoxic effect of erbstatin. Erbstatin increased trypan blue exclusion in cultured LI210 cells. The cytotoxic action of erbstatin was accompanied with shrinking of the cells and internucleosomal DNA fragmentation, characteristics of apoptosis. The DNA fragmentation was induced with other tyrosine kinase inhibitors as well, methyl 2,5-dihydroxycinnamate and herbimycin A. In addition, intracellular tyrosine phosphorylation was inhibited by erbstatin before cell death. Erbstatin-induced DNA fragmentation was prevented by zinc ions, but not by cycloheximide or 12-O-tetradecanoylphorbol 13-acetate (TPA). Thus, erbstatin induced apoptotic cell death in L1210 cells by inhibiting tyrosine kinase.
ASJC Scopus subject areas
- Analytical Chemistry
- Applied Microbiology and Biotechnology
- Molecular Biology
- Organic Chemistry