Anti-Cancer Effects of CIS-Unsaturated Fatty Acids both In Vitro and In Vivo

Abstract

Cis-unsaturated fatty acids (c-UFAs) such as gamma-linolenic acid (GLA), arachidonic acid (AA) and eicosapentenoic acid (EPA) were found to be toxic to human breast tumor cells (ZR-75–1) but not to normal human fibroblasts (41-SK) in vitro. This selective tumoricidal action of GLA, AA and EPA was blocked by anti-oxidants but not by prostaglandin and leukotriene inhibitors suggesting a role of free radicals and lipid peroxidation. On the other hand, LA (linoleic acid), GLA, dihomo GLA (DGLA), EPA and docosahexaenoic acid (DHA) showed cytotoxicity towards human cervical carcinoma cells (HeLa) in vitro. The fatty acid-induced cytotoxic action of HeLa cells could be blocked by antioxidants, calmodulin antagonists, and cyclo- and lipoxygenase inhibitors. These results are in contrast to those observed with ZR-75-1 cells, indicates that though, free radicals are the mediators of the tumoricidal action of fatty acids, the mechanism of their production may be different in different types of tumor cells. In addition intra-tumoral GLA therapy induced substantial decrease in the size of the human gliomas as evidenced by serial CT scan examination. Further, both in vitro and in vivo studies showed that GLA and DGLA can prevent genetic damage induced by radiation and chemicals. These results suggest that specific fatty acids have anti-cancer actions.