Effect of N8-acetylspermidine deacetylase inhibition on the growth of L1210 cells

Abstract

A selective inhibitor of N 8-acetylspermidine deacetylase has been employed to study the role of N 8-acetylspermidine deacetylation in the regulation of L1210 cell growth. This inhibitor, 7-[ N-(3- a mino p ropyl) amino] heptan-2-one (APAH), was found to stimulate the growth of L1210 cells at concentrations between 10 μM and 0.5 mM. Maximum stimulation was seen at 100 μM, resulting in significantly increased rates of cell division and maximum cell density. N 8-Acetylspermidine levels in L1210 cells were shown to increase significantly after the APAH treatment as would be expected for deacetylase inhibition. The effects of deacetylase inhibition were mimicked by addition of N 8-acetylspermidine to the culture medium at concentrations greater than 1 mM as indicated by a subsequent increase in rate of cell growth and maximum cell density. The magnitudes of the increases in growth observed were not large, but this might be expected in cells that are already in a rapid growth phase. Other exogenously added polyamines including N 1-acetylspermidine, spermidine, putrescine, and spermine did not stimulate cell growth. These data suggest that stimulation of cell growth occurs as a consequence of N 8-acetylspermidine accumulation and N 8-acetylspermidine deacetylase inhibition.