Abstract
Polyunsaturated fatty acids (PUFAs) have tumoricidal action, though the exact mechanism of their action is not clear. The results of the present study showed that of all the fatty acids tested, linoleic acid (LA) and α-linolenic acid (ALA) were the most effective in suppressing the growth of normal gastric cells (GES1) at 180 and 200 μM, while gastric carcinoma cells (MGC and SGC) were inhibited at 200 μM. Arachidonic acid (AA) suppressed the growth of GES1, MGC and SGC cells and lower concentrations (120 and 160 μM) of AA were more effective against gastric carcinoma (MGC and SGC) cells compared to normal gastric cells (GES1). Paradoxically, both eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids though are more unsaturated than AA, were less effective compared with LA, ALA and AA in suppressing the growth of both normal and cancer cells. At the concentration used, methotrexate showed much less growth suppressive action compared to all the fatty acids tested. PUFAs-treated cells showed accumulation of lipid droplets. A close association was noted between apoptosis and lipid peroxides formed compared to the ability of normal and tumor cells to generate ROS (reactive oxygen species) and induce SOD (superoxide dismutase activity) in response to fatty acids tested and methotrexate. Both normal and tumor cells generated lipoxin A4 (LXA4) in response to supplementation of fatty acids and methotrexate though no significant correlation was noted between their ability to induce apoptosis and LXA4 formed. These results suggest that PUFAs induced apoptosis of normal gastric and gastric carcinoma cells could, partly, be attributed to lipid peroxidation process.
Highlights
Gastric cancer is the fourth most prevalent malignant disease and the second leading cause of cancer death worldwide [1,2]
GES1 cells were found to be more susceptible to the growth suppressive actions of all the fatty acids tested except DHA compared with MGC and SGC cells
Polyunsaturated fatty acids (PUFAs) induce apoptosis of cells The growth inhibitory action of PUFAs and methotrexate on GES1, MGC and SGC cells is due to their ability to induce apoptosis as determined by flow cytometry
Summary
Gastric cancer is the fourth most prevalent malignant disease and the second leading cause of cancer death worldwide [1,2]. The long-chain metabolites of EFAs: Previously, we and others showed that gammalinolenic acid (GLA, 18:3 ω-6), AA, EPA and DHA could be selectively cytotoxic to various tumor cells in vitro and in vivo [3,4,5,6,7,8,9,10,11,12,13,14,15,16] Many of these studies were performed without taking into consideration the action(s) of these fatty acids on respective normal cells. We studied fatty acid profile of cells supplemented with various fatty acids and their influence on the formation of lipid peroxides and free radical generation
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