The Effects of n-3 Fatty Acids and Bexarotene on Breast Cancer Cell Progression

Abstract

Breast cancer cell growth can be inhibited in vivo by retinoid X receptor (RXR) specific retinoids. In both animal and cell culture studies, omega-3 fatty acids share growth regulatory effects similar to those of RXR specific retinoids (rexinoids). One synthetic rexinoid, bexarotene (LCD 1069, Targretin), is used clinically to treat cancer patients. Of concern is that some patients are unable to tolerate high doses of such treatment drugs. We hypothesized that n-3 fatty acids and bexarotene may work synergistically to slow breast cancer cell growth. To test our hypothesis, we used MCF-7 human mammary carcinoma cells and an in vitro cell culture model. We investigated the relationship between the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) alone and in conjunction with bexarotene in slowing MCF-7 cell growth. Following a 72 hr incubation with the respective treatments, bexarotene enhanced cell growth (p < 0.05) while DHA showed a strong growth inhibitory effect which was not enhanced by the addition of bexarotene (p < 0.05). EPA alone was not effective in altering cell growth (p < 0.05). Interestingly, when combined with bexarotene, EPA was more effective at slowing cell growth than when cells received EPA alone. Thus, select omega-3 fatty acids alone are more effective than bexarotene in slowing MCF-7 cell progression. However, the use of the RXR-selective retinoids may enhance the growth regulatory mechanisms of the fatty acid EPA.