Induction of programmed cell death in human breast cancer cells by an unsymmetrically alkylated polyamine analogue

• Published in: Cancer research (Chicago, Ill.) Vol. 55; no. 15; pp. 3233 - 3236
• Main Authors: MCCLOSKEY, D. E, CASERO, R. A, DAVIDSON, N. E, WOSTER, P. M
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.1995
• Subjects: Acetyltransferases - analysis; Antineoplastic agents; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Breast Neoplasms - enzymology; Breast Neoplasms - pathology; Breast Neoplasms - physiopathology; Cell Division - drug effects; DNA, Neoplasm - drug effects; General aspects; Humans; Medical sciences; Neoplasms, Hormone-Dependent - enzymology; Neoplasms, Hormone-Dependent - pathology; Neoplasms, Hormone-Dependent - physiopathology; Pharmacology. Drug treatments; Polyamines - pharmacology; RNA, Messenger - analysis; Tumor Cells, Cultured; Antineoplastic agent; Human; Mammary gland diseases; Polyamine; Cell death; Analog; Established cell line; Mammary gland; Malignant tumor; Mechanism of action; In vitro; Tumor cell
• ISSN: 0008-5472; 1538-7445

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 microM 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.