Induction of programmed cell death in human breast cancer cells by an unsymmetrically alkylated polyamine analogue.
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.
McCloskey
D E
DE
Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Casero
R A
RA
Woster
P M
PM
Davidson
N E
NE
D000123:Acetyltransferases / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D011073:Polyamines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011073:Polyamines; D012333:RNA, Messenger; D000099228:Diamine N-Acetyltransferase; C083629:N(1)-ethyl-N-(11)-((cyclopropyl)methyl)-4,8-diazaundecane-1,11-diamine