A study into the different mechanisms of anti-cancer effect of docosahexanoic acid in colon cancer cells

Abstract

Colon cancer is a leading cause of cancer mortality in the developed world. Epidemiological evidence suggests that n-3 polyunsaturated fatty acids (PUFAs) may protect against colon cancer. In this study we show that docosahexanoic acid (DHA)(22:6, n-3), induced caspase-dependent apoptosis in HT-29 colon cancer cells. DHA activated JNK, ERK and p38 MAPKs. Inhibition of JNK either by SP600125 or by overexpression of the dominant-nagative mutants significantly repressed DHA-induced apoptosis. DHA also induced oxidative stress but JNK activity and apoptosis were independent of the ROS generation. We further show that DHA activated PPARgamma and inhibited TNFalpha-induced COX-2 expression. Repressing the PPARgamma protein expression de creased the inhibitory effect of DHA on COX-2 expression. However, there were no significant changes in cell death indicating that DHA induced apoptosis through PPARgamma-independent pathway. In conclusion, this study provides an insight in to the different pathways involved anti-cancinogenic role of DHA in colon cancer.