INDUCTION OF BIMODAL PROGRAMMED CELL-DEATH IN MALIGNANT-CELLS BY THE DERIVATIVE UKRAIN (NSC-631570)

Selective induction of malignant cell death is one of the major goals of effective and safe chemotherapy Recent developments in the understa nding of programmed cell death (PCD) or apoptosis are expected to prov ide new leads for a safer chemotherapy. The authors investigated wheth er the semisynthetic alkaloid thiophosphoric acid derivative Ukrain (N SC-631570) could induce PCD or apoptosis in human K562 leukaemia cells . Results showed that Ukrain induced two distinct modalities of cell d eath programmes. One modality corresponded morphologically to classica l apoptosis or PCD characterized by blebbing and shedding of membrane vesicles with concomitant Cr-51 release; however, the Ukrain-induced a poptosis was not associated with the characteristic nuclear DNA fragme ntation. Higher concentrations of Ukrain induced a second cell death p rogramme characterized by cell surface blister formation, high specifi c Cr-51 release and extensive DNA polyploidy. These two cell death pro grammes are distinct from each other in that they are interphased by a silent period characterized by normal cell morphology and reduced spe cific Cr-51 release.