PUFA-induced stress in cancer cells –autophagy as a potential determinant for cell survival

Abstract

Polyunsaturated fatty acids (PUFAs) show diverse effects on cancer cells. The explanation to why some cancer cells seem to be sensitive of PUFAs and some do not is, however, still a debated topic. Autophagy is a disease preventive process that can protect cells from cellular stress situations. In this study, we investigate whether DHA can induce the autophagic process and whether differences in regulation of autophagy can explain why some cancer cells are sensitive to DHA and some are not. We find that autophagy is not induced in DHA exposed cancer cells that have constitutively elevated levels of AKT. Because of the inability to induce autophagy, these cells are severely growth inhibited, and perhaps apoptotic, when exposed to DHA. Cancer cells with normal AKT regulation are, on contrary, able to induce autophagy and survive DHA-induced stress. Furthermore, DHA induces a network of alterations in gene expression. We have initiated experiments where some of the early response genes are expressed in an inducible manner to start to uncover their individual role in the network.