The response of human carcinoma cell lines to gamma-linolenic acid with special reference to the effects of agents which influence prostaglandin and thromboxane synthesis.
Recently, addition of gamma linolenic acid (GLA) which is a precursor of prostaglandin E1 (PGE1) to cell cultures, has been shown to inhibit growth of various carcinoma cells (1,2,3,4). These findings are consistent with Horrobin's proposal that some of the metabolic abnormalities of malignant cells may be due to deficiencies of certain prostanoids. To determine whether the observed effects of GLA are in fact mediated by increasing levels of its metabolites, this study investigated the influence of various inhibitors and stimulants of prostaglandin (PG) synthesis on the effects of GLA on carcinoma cells in vitro. Most of the agents used (aspirin, imidazole, lithium carbonate and ascorbic acid) produced results consistent with the idea that elevation of levels of thromboxane A2 (TxA2) and/or PGE1 may be important as regards the actions of GLA. In sharp contrast was the result obtained with indomethacin. This drug, which could be expected to block conversion of GLA to PGE1 and therefore protect cells against the effects of GLA, actually exaggerated the effects of this fatty acid, thereby causing cell death and desquamation.
Botha
J H
JH
Robinson
K M
KM
Leary
W P
WP
D000527:Alprostadil; D001241:Aspirin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008042:Linolenic Acids / Q000172:deficiency / Q000378:metabolism / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism; D013931:Thromboxanes / Q000096:biosynthesis*; D017965:gamma-Linolenic Acid
D007093:Imidazoles; D008042:Linolenic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D013931:Thromboxanes; D013928:Thromboxane A2; D017965:gamma-Linolenic Acid; C029899:imidazole; D000527:Alprostadil; D001241:Aspirin; D007213:Indomethacin