Upregulation of heat shock protein 27 confers resistance to actinomycin D ‐induced apoptosis in cancer cells

Actinomycin  D (Act  D ) is a general transcriptional inhibitor that is approved for the treatment of sarcomas, and W ilms, germ cell and trophoblastic tumors. Little is known about the molecular mechanisms that dictate the sensitivity of cancer cells to Act  D . In this study, we investigated the effects of Act  D on heat shock proteins ( HSP s) and the expression and roles of HSP 27 in Act  D ‐induced cancer cell apoptosis. We show that Act  D upregulates HSP 27 and HSP 70 expression in cancer cells, whereas it inhibits HSP 90 expression. The upregulation of HSP 27 by Act  D is not attributable to changes in HSP27 transcription or HSP 27 synthesis. HSP 27 knockdown leads to an increase in Act  D ‐induced caspase 3 and caspase 7 cleavage, and sensitizes rhabdosarcoma cells and breast cancer cells to Act  D ‐induced apoptosis. We conclude that upregulation of HSP 27 represents an adaptive response that compromises the anticancer activity of Act  D .