Premium
Suppression of W256 carcinosarcoma cell apoptosis by arachidonic acid and other polyunsaturated fatty acids
Author(s) -
Tang Dean G.,
Guan KunLiang,
Li Li,
Honn Kenneth V.,
Chen Yong Q.,
Rice Renee L.,
Taylor John D.,
Porter Arthur T.
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970917)72:6<1078::aid-ijc24>3.0.co;2-#
Subject(s) - nordihydroguaiaretic acid , apoptosis , arachidonic acid , programmed cell death , lipoxygenase , linoleic acid , biology , polyunsaturated fatty acid , chemistry , biochemistry , fatty acid , enzyme
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 time‐ and dose‐dependent fashion, suppressed NDGA‐induced W256 cell apoptosis as well as DNA fragmentation, with the maximal effect observed at approximately 25 μM. Mobilization of endogenous AA by calcium ionophore A23187 provided an even stronger and longer‐lasting protection against NDGA‐caused cell death. The A23187 effect on AA release as well as W256 cell death can be blocked by bromophenacyl bromide, thus suggesting involvement of phospholipase A 2 activation. Serum withdrawal similarly caused W256 cells to undergo typical apoptosis, which was not rescued by several growth factors commonly found in serum. However, exogenous AA suppressed serum starvation‐induced W256 cell apoptosis and significantly extended cell survival in a dose‐dependent manner. Lipoxygenase products, 12(S)‐ and 15(S)‐, but not 5(S)‐hydroxyeicosatetraenoic acid (HETE), in a dose‐dependent fashion, also prevented both NDGA‐ and serum‐starvation‐induced W256 cell apoptosis. AA appears to suppress W256 cell apoptosis via distinct signaling pathway(s) since it does not prevent cell death triggered by several other inducers. Examination of a panel of polyunsaturated fatty acids revealed that α‐linolenic and linoleic acid can also suppress NDGA‐induced W256 cell apoptosis. Our data suggest that AA and other polyunsaturated fatty acids and/or their metabolites may enhance tumor growth not only by promoting cell proliferation but also by suppressing apoptosis. Int. J. Cancer 72:1078–1087, 1997. © 1997 Wiley‐Liss, Inc.