Effects of polyunsaturated fatty acids on the growth of gastric cancer cells in vitro
Effects of polyunsaturated fatty acids on the growth of gastric cancer cells in vitro
Year: 2013
Authors: Dai, J. Shen, J. Pan, W. Shen, S. Das, U.N.
Publication Name: Lipids Health Dis.
Publication Details: Volume 12; Page 71
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 alpha linolenic acid (ALA) were the most effective in suppressing the growth of normal gastric cells (GES1) at 180 and 200 microM, while gastric carcinoma cells (MGC and SGC) were inhibited at 200 microM. Arachidonic acid (AA) suppressed the growth of GES1, MGC and SGC cells and lower concentrations (120 and 160 microM 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. (Authors abstract). Gastric cancer is the fourth most prevalent malignant disease and the second leading cause of cancer death worldwide. There is considerable evidence to suggest that essential fatty acids (EFAs): cis linoleic acid (LA, 18:2, n 6) and alpha linolenic acid (ALA, 18:3, n 3) and their metabolites exert significant inhibitory action on the growth of tumor cells both in vitro and in vivo. It has been documented that tumor cells have decreased activity of delta 6 and delta 5 desaturases that are essential for the metabolism of LA and ALA to their respective long chain metabolites. In the present study, the effect of various long chain fatty acids on the growth of gastric carcinoma cells and their respective normal gastric cells was examined. The fatty acid profile of cells supplemented with various fatty acids and their influence on the formation of lipid peroxides and free radical generation is also reported. The amounts of LXA4 generated by normal and gastric cancer cells when supplemented with various PUFAs was assessed.
PUFAs have cytotoxic action on tumor cells. The suggested mechanism(s) of the tumoricidal action of PUFAs include: (a) increased generation of ROS; (b) enhanced lipid peroxidation resulting in accumulation of toxic lipid peroxide products in the cells that ultimately results in cell death; (c) activation of caspases; (d) activation of PPARs; (e) modulating gene per anti oncogene expression, and (f) induction of chromosomal damage. It is doubtful whether PUFAs are toxic only to tumor cells without being cytotoxic to relevant normal cells. It is evident from the results of the present study that all the PUFAs tested (LA, AA, ALA, EPA and DHA) and methotrexate were able to induce apoptosis of the three types of cells tested (both normal and gastric cancer cells) and showed very little differential action on normal and tumor cells. Cell viability was affected only at higher concentrations (180 and 200 microM) of various PUFAs suggesting that both normal (GES1) and gastric tumor (MGC and SGC) cells are relatively resistant to the cytotoxic action of fatty acids tested. One distinct observation that was made in the present study was the accumulation of lipid droplets in both normal GES1 and gastric tumor cells MGC and SGC that were supplemented with 180 microM of various fatty acids for 48 hours. In general, ALA, AA, EPA and DHA supplemented cells showed more number of lipid droplets compared to the control and methotrexate treated cells. Studies into the mechanism(s) of cytotoxic action of PUFAs and methotrexate showed little correlation among cytotoxic action of PUFAs and methotrexate on GES1, MGC and SGC cells; production of ROS, formation of lipid peroxides, changes in the levels of SOD and LXA4 in these cells, suggesting that none of these mechanisms seem to be solely responsible for the cytotoxic action of fatty acids and methotrexate tested. Of all, only accuulation lipid peroxides seems to show the most correlation between the cytotoxic action of PUFAs and methotrexate on GES1, MGC and SGC cells and apoptosis. This indicates that formation of lipid peroxides in the normal and cancer cells on supplementation with various PUFAs and anti cancer drug (methotrexate in the present instance) are the best predictors of their cytotoxic action. (Editors comments)
PUFAs have cytotoxic action on tumor cells. The suggested mechanism(s) of the tumoricidal action of PUFAs include: (a) increased generation of ROS; (b) enhanced lipid peroxidation resulting in accumulation of toxic lipid peroxide products in the cells that ultimately results in cell death; (c) activation of caspases; (d) activation of PPARs; (e) modulating gene per anti oncogene expression, and (f) induction of chromosomal damage. It is doubtful whether PUFAs are toxic only to tumor cells without being cytotoxic to relevant normal cells. It is evident from the results of the present study that all the PUFAs tested (LA, AA, ALA, EPA and DHA) and methotrexate were able to induce apoptosis of the three types of cells tested (both normal and gastric cancer cells) and showed very little differential action on normal and tumor cells. Cell viability was affected only at higher concentrations (180 and 200 microM) of various PUFAs suggesting that both normal (GES1) and gastric tumor (MGC and SGC) cells are relatively resistant to the cytotoxic action of fatty acids tested. One distinct observation that was made in the present study was the accumulation of lipid droplets in both normal GES1 and gastric tumor cells MGC and SGC that were supplemented with 180 microM of various fatty acids for 48 hours. In general, ALA, AA, EPA and DHA supplemented cells showed more number of lipid droplets compared to the control and methotrexate treated cells. Studies into the mechanism(s) of cytotoxic action of PUFAs and methotrexate showed little correlation among cytotoxic action of PUFAs and methotrexate on GES1, MGC and SGC cells; production of ROS, formation of lipid peroxides, changes in the levels of SOD and LXA4 in these cells, suggesting that none of these mechanisms seem to be solely responsible for the cytotoxic action of fatty acids and methotrexate tested. Of all, only accuulation lipid peroxides seems to show the most correlation between the cytotoxic action of PUFAs and methotrexate on GES1, MGC and SGC cells and apoptosis. This indicates that formation of lipid peroxides in the normal and cancer cells on supplementation with various PUFAs and anti cancer drug (methotrexate in the present instance) are the best predictors of their cytotoxic action. (Editors comments)
