1-Oleoyl 2-acetyl glycerol inhibits differentiation of TPA-sensitive but not of TPA-resistant Friend cells.

Recent studies have shown that diacylglycerols mimic several effects of 12-O-tetradecanoylphorbol 13-acetate (TPA) on cultured cells and suggest that diacylglycerols are the endogenous functional analogues of phorbol esters. However, all such studies have been of short duration, and although a single application of diacylglycerol induces these effects, tumour promotion usually requires long and repeated application of tumour-promoting agents. Here we investigated the effect of 1-oleoyl 2-acetyl glycerol (OAG) on differentiation of Friend erythroleukaemia cells (FELC), since TPA must be present continuously to inhibit differentiation in this system throughout the experiment. We also studied the effects of OAG in both TPA-sensitive and TPA-resistant clones, to investigate whether OAG and TPA have a similar mode of action. We found a dose-dependent inhibition of differentiation by OAG in the TPA-sensitive clone, but not in the TPA-resistant clone. Repeated treatment was necessary to achieve these results; almost complete inhibition could be obtained when OAG was applied 7 times/day for 3.5 days at 3 micrograms/ml per application, whereas a single application of OAG at a higher dose had no effect. Protein kinase C, which is believed to be the common target of OAG and TPA, was present in both TPA-sensitive and TPA-resistant FELC clones. These results suggest that OAG mimics the long-term effect of TPA and that the mechanism by which FELC clones resist TPA and OAG is not a lack or functional deficiency of protein kinase C.