Studies on a novel DNA polymerase inhibitor group, synthetic sulfoquinovosylacylglycerols: inhibitory action on cell proliferation

Some chemically synthesized sulfoquinovosylmonoacylglycerols (SQMG)-sulfoqu inovosyldiacylglycerols (SQDG) have been reported to selectively and strong ly inhibit the activities of mammalian DNA polymerases alpha and beta in vi tro. In this study, using human cancer cell lines, we investigated the effe cts of SQMG-SQDG on the DNA polymerase in the cells. In the presence of n-d ecane, the IC50 values on cell growth were approximately 1-5 mu M for SQMG and about 0.3-1 mu M for SQDG. The values were almost the same as the in vi tro enzyme inhibitory levels. The cell lines were arrested in early S-phase by SQMG-SQDG at the concentrations of 0.1-4.7 mu M in a manner dependent o n incubation time, suggesting that SQMG-SQDG blocked the primary step of DN A replication by inhibiting DNA polymerase, possibly alpha-type. We also de monstrated the localization of SQMG in the cell using the fluorescent SQMG analog, SQMG alpha-NBDD, which was synthesized in our laboratory. SQMG alph a-NBDD was localized in the nucleus and on the nuclear surface, but the bin ding site seemed not to be the DNA/chromatin. suggesting that the SQMG-SQDG might interact with molecules located close to the DNA/chromatin and on th e nuclear surface. These results suggested a correlation between the in vit ro biochemical action of the SQMG-SQDGs and their intracellular mode of act ion. (C) 2000 Elsevier Science B.V. All rights reserved.