INDUCTION OF PROGRAMMED CELL-DEATH IN HUMAN BREAST-CANCER CELLS BY ANUNSYMMETRICALLY ALKYLATED POLYAMINE ANALOG

The need for antineoplastic compounds with novel mechanisms of action is great. One such agent is the recently synthesized polyamine analogu e ethyl-N-11-((cyclopropyl)methyl)-4,8-diazaundecane (CPENSpm). Exposu re of hormone-dependent and -independent human breast cancer cells to 0.1-10 mu M CPENSpm led to both growth inhibition and induction of pro grammed cell death, Fragmentation of DNA to high molecular weight frag ments and oligonucleosomal-sized fragments, bath characteristic of pro grammed cell death, was determined to be time and concentration depend ent. Depletion of natural polyamine pools and accumulation of the anal ogue was also demonstrated. These data provide the first evidence that a polyamine analogue induces programmed cell death.