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

LIEPINS A.^1*, NOWICKY J.W.², BUSTAMANTE J.O.³, LAM E.¹

1) Faculty of Medicine, Memorial University, St. John's, Newfoundland, A1B 3V6, Canada.
2) Ukrainian Anti-Cancer Institute, Margaretenstrasse 7, 1040 Vienna, Austria.
3) Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, 21201-1559, USA.

* Author to whom correspondence should be addressed.

Summary: Selective induction of malignant cell death is one of the major goals of effective and safe chemotherapy. Recent developments in the understanding of programmed cell death (PCD) or apoptosis are expected to provide new leads for a safer chemotherapy. The authors investigated whether the semisynthetic alkaloid thiophosphoric acid derivative Ukrain (NSC-631570) could induce PCD or apoptosis in human K562 leukaemia cells. Results showed that Ukrain induced two distinct modalities of cell death programmes. One modality corresponded morphologically to classical apoptosis or PCD characterized by blebbing and shedding of membrane vesicles with concomitant ⁵¹Cr release; however, the Ukrain-induced apoptosis was not associated with the characteristic nuclear DNA fragmentation. Higher concentrations of Ukrain induced a second cell death programme characterized by cell surface blister formation, high specific ⁵¹Cr release and extensive DNA polyploidy. These two cell death programmes are distinct from each other in that they are interphased by a silent period characterized by normal cell morphology and reduced specific ⁵¹Cr release.