SUPPRESSION OF W256 CARCINOSARCOMA CELL APOPTOSIS BY ARACHIDONIC-ACIDAND OTHER POLYUNSATURATED FATTY-ACIDS

Serum-cultured rat W256 carcinosarcoma cells of the monocytoid origin undergo rapid apoptosis in response to the lipoxygenase inhibitor NDGA (nordihydroguaiaretic acid). Exogenous arachidonic acid (AA), in a ti me-and dose-dependent fashion, suppressed NDGA-induced W256 cell apopt osis as well as DNA fragmentation, with the maximal effect observed at approximately 25 mu M. Mobilization of endogenous AA by calcium ionop hore A23187 provided an even stronger and longer-lasting protection ag ainst NDGA-caused cell death. The A23187 effect on AA release as well as W256 cell death can be blocked by bromophenacyl bromide, thus sugge sting involvement of phospholipase A(2) activation. Serum withdrawal s imilarly caused W256 cells to undergo typical apoptosis, which was not rescued by several growth factors commonly found in serum. However, e xogenous AA suppressed serum starvation-induced W256 cell apoptosis an d significantly extended cell survival in a dose-dependent manner. Lip oxygenase products, 12(S)- and 15(S)-, but not S(S)-hydroxyeicosatetra enoic acid (HETE), in a dose-dependent fashion, also prevented both ND GA- and serum-starvation-induced W256 cell apoptosis. AA appears to su ppress W256 cell apoptosis via distinct signaling pathway(s) since it does not prevent cell death triggered by several other inducers. Exami nation of a panel of polyunsaturated fatty acids revealed that alpha-l inolenic and linoleic acid can also suppress NDGA-induced W256 cell ap optosis. Our data suggest that AA and other polyunsaturated fatty acid s and/or their metabolites may enhance tumor growth not only by promot ing cell proliferation but also by suppressing apoptosis. (C) 1997 Wil ey-Liss, Inc.