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

The Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 [D. E. M., R. A. C., N. E. D.], and Wayne State University, Detroit, Michigan 48202 [P. M. W.]

The need for antineoplastic compounds with novel mechanisms of action is great. One such agent is the recently synthesized polyamine analogue N¹-ethyl-N¹¹-((cyclopropyl)methyl)-4,8-diazaundecane(CPENSpm). Exposure of hormone-dependent and -independent human breast cancer cells to 0.1–10 µM CPENSpm led to both growth inhibition and induction of programmed cell death. Fragmentation of DNA to high molecular weight fragments and oligonucleosomal-sized fragments, both characteristic of programmed 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.

¹ This work was supported by NIH grants CA09071, CA57545, CA/ES66204, CA63552, and CA51085, and the Susan G. Komen Foundation.

² To whom requests for reprints should be addressed, at Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, 422 N. Bond Street, Baltimore, MD 21231.

Received 5/31/95. Accepted 6/21/95.

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