DIFFERENT EFFECTS OF 4-(4'-CHLOROBENZYLOXY)BENZOIC ACID (MII) ON LIPID SYNTHESIS AND CELL GROWTH IN HUMAN AND MOUSE SKIN FIBROBLASTS

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The effect of 4-(4'-chlorobenzyloxy)benzoic acid (MII), a metabolite of a new hypolipidemic agent 4-(4'-chlorobenzyloxy)benzyl nicotinate (KCD-232), on lipid synthesis and cell growth was studied in human skin fibroblasts (HSF), mouse skin fibroblasts (MSF) and other rodent-derived cell. MII inhibited sterol synthesis in both HSF and MSF in a dose dependent manner. The drug also suppressed fatty acid synthesis, weakly in HSF and markedly in MSF. The growth of MSF was inhibited by MII in a dose dependent manner, whereas that of HSF was not inhibited at all by MII up to 1 mM. The MII-mediated inhibition of MSF growth was not prevented by the addition to the medium of intermediates of the cholesterol synthetic pathway, i.e., mevalonate, squalene or lanosterol. Furthermore, the growth of several cell lines derived from rodents (L, CHL and AH109A cells) was suppressed by MII. These results suggested a possibility that the different effects of MII on the growth of HSF and MSF might be due partly to differences in the effect of MII on fatty acid synthesis between human and rodent cells.
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