STAUROSPORINE ENHANCED BENZAMIDE RIBOSIDE-INDUCED APOPTOSIS IN HUMAN MULTIDRUG-RESISTANT PROMYELOCYTIC LEUKEMIA-CELLS (HL-60 VCR) IN-VITRO/

The inosine monophosphate (IMP) dehydrogenase inhibitor benzamide ribo side (BR) induced apoptosis (detected with the aid of flow cytometric identification of cells with sub-G(0) DNA content and increased side a ngle light scatter) equally or slightly more intensively in the multid rug-resistant human promyelocytic leukemia cell line (HL-60/VCR: MDR-1 gene, Pgp positive) in comparison with the parental drug sensitive HL -60 cells. Staurosporine alone induced relatively low level of apoptos is in parental HL-60 cells but higher level (approximately 35%) of apo ptosis in multidrug-resistant HL-60/VCR cells after 24 hour induction. The combination of benzamide riboside and staurosporine induced in bo th drug-sensitive and drug-resistant HL-60 cells a marked proportion o f apoptotic cells already after short (6 hour) induction (more than 30 % of apoptotic cells).