Biochemical and growth-modulatory effects of the new S-adenosylmethionine decarboxylase inhibitor CGP 48664 in malignant and immortalized normal human breast epithelial cells in culture

摘要: CGP 48664 [4-aminoindanon-1-(2′-amidino)hydrazone dihydrochloride monohydrate] is a newly introduced inhibitor of S-adenosyltnethionine decarboxylase (SAMDC) with increased selectivity action and reduced toxichy. We analyzed the biochemical antiproliferative effects this compound in panel hormone-dependent (3 clones MCF-7, T47D) -independent (MDA-MB-231, BT-20) human breast cancer cell lines culture. For comparison, we also tested its spontaneously immortalized epithelial line MCF-10A. All were highly sensitive to growth-inhibitory effect an IC50 between 0.1 0.5 μM. A dose-dependent bell-shaped increase SAMDC was observed normal malignant cells resulting from enzyme stabilization by as supported Western blot analysis. While omithine (ODC) activity consistently increased, on spermidine J. spermine N′acetyltransferase (SSAT) variable lines. In contrast, SSAT level MCF-10A derivative partially transformed mutated ras oncogene. As expected, cellular putrescine levels markedly administration, whereas contents reduced. However, degree reduction usually only moderate. Furthermore, exogenous polyamine administration relatively ineffective rescuing MCF-7 cells, while exerting more complete rescue MDA-MB-231 line. conclude that exerts potent mammary may not always be entirely mediated through pathway. © 1995 Wiley-Liss, Inc.