Enhancement of carcinostatic activity of omega-hydroxy fatty acids by their esterification through increased uptake into tumor cells

Diverse omega-hydroxy fatty acids (omegaHFAs) and their derivatives were examined for their ability to diminish the cell viability of Ehrlich ascites tumor cells by the mitochondrial dehydrogenase-based WST-1 assay and trypan blue dye exclusion assay. Of the diverse omegaHFAs, hydroxyhexadecanoic acid (omegaH16:0) was appreciably carcinostatic, and hydroxypentadecanoic acid (omegaH15:0) or hydroxypentadecenoic acid (omegaH15:1) was weakly carcinostatic at a dose of 100 micro M, whereas hydroxydodecanoic acid (omegaH12:0) and hydroxyhexadecenoic acid (omegaH16:1) acid were scarcely carcinostatic at the same dose. In contrast their sodium salt derivatives except omegaH16:0 were not carcinostatic. Enhancement of the carcinostatic activity was markedly exerted by ethylesterization of omegaHFAs with the saturated fatty moiety such as omegaH16:0 and omegaH15:0, whereas ethylesters of the unsaturated omegaHFAs such as omegaH15:1 and omegaH16:1 were weakly carcinostatic. Thus intramolecular introduction of a double bond was shown to weaken the carcinostatic activity in case of either omegaHFAs or their ethylester, being in contrast to the conventional knowledge concerning the enhancement of carcinostatic activities of non-hydroxy fatty acids appendant with more double bonds. The intracellular uptake amount of each omegaHFA as quantified by gas chromatography was the following order: omegaH16:0 ethylester (10.1 pg/cell) > omegaH15:0 ethylester (6.4 pg/cell) > omegaH16:0 (3.4 pg/cell) > omegaH15:0 (2.8 pg/cell), which accords with the order of carcinostatic activities of four saturated omegaHFAs in contrast to discord between both the orders for unsaturated omegaHFAs which could be scarcely detected as the intact form within cells. The results indicate that enhancement of carcinostatic activity of omegaH16:0 by ethylesterization was attributed to an appreciable correlation between intracellular uptake amounts and carcinostatic activities for diverse omegaHFAs with saturated fatty moiety, being not true for unsaturated omegaHFAs.