Effects of the polyamine analogs BE-3-7-3, 3-8-3, and BE-3-8-3 on human brain tumor cell growth and survival.
Based on computer modeling, physicochemical studies of spermine-DNA interactions, and cell culture experiments, we hypothesized that polyamine analogs with hydrocarbon chain lengths differing from natural polyamines and a stronger affinity for nucleic acids than spermine should have a cellular antiproliferative effect. We tested three spermine analogs with long hydrocarbon chains, 1,16-diamino-4,12-diazahexadecane (3-8-3), 1,16-bis(ethyl)amino-4,12-diazahexadecane (BE-3-8-3), and 1,15-bis(ethyl)amino-4,11-diazapentadecane (BE-3-7-3) in human brain tumor cell lines U-251 MG, SF-126, and SF-188. Analog concentrations < or = 5 microM inhibited growth and colony-forming efficiency in each cell line by treatment day 5, with significant decreases in putrescine and spermidine, but not spermine, levels. These findings suggest that potentially cytotoxic polyamine analogs can be specified on the basis of their hydrocarbon chain length and DNA affinity.
Basu
H S
HS
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143.
Pellarin
M
M
Feuerstein
B G
BG
Deen
D F
DF
Marton
L J
LJ
D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D011700:Putrescine / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D013096:Spermine; D013095:Spermidine; D011700:Putrescine