Conjugated linoleic acid and cancer

Fats in general have been implicated in the etiology of many forms of cancer, yet evidence is accumulating that certain types of fatty acids have anticancer properties, of which conjugate linoleic acd (CLA) is the major one. Inhibitory effects of CLA against carcinogenesis have been demonstrated in a variety of cell type, sites, and animal models including mammary gland, skin, colon, prostate, and forestomach of rats, humans, mice, and hamsters. In contrast to the hundreds of phytochemicals possessing varying degrees of anticancer properties, CLA is unique in that it is a FA, is found in highest amounts in food products derived from ruminants, and is safe at dietary levels. It is believed that CLA is involved in a variety of biological events in all three stages of carcinogenesis viz initiation, promotion, and progression. It is also believed that the effects vary with the specific isomers of CLA and the type and site of the cell/organ as well as the stage of tumerogenesis. Overall, the effects of CLA are related to inhibition of growth and proliferation, induction of apoptosis, and diminishing branching and reducing the density of ductal system of the cancerous cells.

It was found that mammary tumor incidence as well as mass and weight were reduced in rats fed CLA. Exposure to 1% CLA during the early preweaning and pubertal period only was sufficient to reduce the subsequent methylnitrosurea induced tumerogenesis in rats, which may have further implications in cancer prevention in humans once it is proven with clinical case-control studies. It has also been found that CLA decreased mammary tumor incidence by 50% and tumor number by 45% in rats fed CLA at 0.8% of the diet. By way of comparison, the efficacy of fish oil, which is also an anticancer agent and which is not plant derived, is 100 times lower than that of CLA. It was found that cell number was decreased up to 90% and lipid peroxidation increased by 15-fold following incubation of breast cancer cells for 8 days with increasing levels of milk, yielding CLA concentrations between 16.9 and 22.6 ppm. Moreover, CLA has not only been found altering mammary tumor incidence, but also affecting later stages, especially metastasis as effectively as indomethacin, a known suppressor of tumor growth and metastasis in murine mammary tumors. It supports the notion that CLA may be efficacious in preventing the development and recurrence of some cancers as well as suppressing the growth of residual disease. 

There are many different isomers of CLA, of which t-10, c-12 CLA and c-9, c-11 CLA are the major ones. Using an apoptotic marker, c-9, t-11 CLA was found to be the better apoptotic inducer compared with t-10, c-12 or a mixture of c-9, t-11 CLA and t-10, c-12 isomers both in breast cancer cell lines. This is in contrast to some other findings on colorectal and prostate cancer cells where t-10, c-12 CLA led to an apoptotic response. In another experiment, c-9, t-11 CLA also turned out to be the best radiosensitizer compared with t-10, c-12 or a mixture of c-9, t-11 CLA and t-10, c-12 isomers. The radiosensitizing property of c-9, t-11 CLA further supports its potential as an agent to improve radiotherapy against breast carcinoma. Regardless, the effects of specific isomer(s) of CLA responsible for anticancer properties are not conclusive nor their mode of action has been well understood.