Abstract

The essential fatty acids, because of their methylene-interrupted double bonds, are highly susceptible to lipid peroxidation. This is a complex process that under appropriate conditions has the characteristics of a chain reaction. During the process, reactive radicals containing oxygen and oxygenated lipids are produced, eventually giving rise to a variety of complex breakdown products including alkenals and aldehydes. The rate of lipid peroxidation is often crudely monitored by estimating products that will react with thiobarbituric acid (TBA-reactive material or TBARM). Most agents currently used in cancer therapy initiate lipid peroxidation: this is usually considered to be a side effect, but the possibility that this is the main anticancer action must be seriously considered. Cancer cells, as compared with normal cells, are resistant to lipid peroxidation. Even normal cells during periods of cell division are resistant to peroxidation. The resistance to peroxidation of cancer cells is due in part to lack of 6-desaturated essential fatty acid (EFA) substrates. Impaired or absent 6-desaturation of EFAS in the cancer cells contributes to this situation. Many cancer cells also contain increased levels of antioxidants, including vitamin E and oleic acid. The origin of these elevated levels is uncertain: oleic acid always accumulates when levels of EFAs are reduced, and vitamin E may accumulate because of an absence of EFAS by which it may be consumed. Addition of 6-desaturated EFAS to cancer cells causes cell death, but normal cells are largely unaffected. EFAS with 3 and 4 double bonds are the most effective, followed by EFAS with 5 double bonds. EFAS with either 2 or 6 double bonds are relatively ineffective. The cell death is associated with a surge of lipid peroxidation and of superoxide formation, which does not occur in normal cells exposed to EFAs. Over 20 human cancer cell lines have now been shown to respond to EFAs in the same way. Administration of gamma-linolenic acid (GLA) in the form of evening primrose oil to animals with various types of experimental cancer has inhibited growth of the tumours. Selective damage to cancer cells without harming normal cells can now be achieved both in vitro and in vivo by using appropriate EFAs and deserves clinical exploration.