Induction of Programmed Cell Death in Human Breast Cancer Cells by an Unsymmetrically Alkylated Polyamine Analogue1

The need for antineoplastic compounds with novel mechanisms of ac tion is great. One such agent is the recently synthesized polyamine analogue /V'-ethyl-A'n-((cyclopropyl)methyl)-4,8-diazaundecane (CPENSpm). Expo sure of hormone-dependent and -independent human breast cancer cells to 0.1-10 UM 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, both characteristic of pro grammed cell death, was determined to be time and concentration dependent Depletion of natural polyamine pools and accumulation of the analogue was also demonstrated. These data provide the first evidence that a polyamine analogue induces programmed cell death.