Abstract 1612: The effect of docosahexaenoic acid on androgen-dependent and androgen-independent prostate tumors in combination with abiraterone and enzalutamide

Standard treatments for prostate cancer typically involve androgen deprivation therapy (ADT). In later stages of prostate cancer, the tumor typically evolves to become insensitive to ADT, otherwise known as castration-resistant prostate cancer (CRPC). Despite being hormone-insensitive, CRPC has been shown to respond to both abiraterone and enzalutamide. Although both treatments deprive the tumor of androgens, they both display different mechanisms of action. Abiraterone inhibits androgen production, and enzalutamide acts by interrupting the binding of androgens to the androgen receptor. Studies in our laboratory have shown that docosahexaenoic acid (DHA; C22:6, n-3), a long chain omega-3 polyunsaturated fatty acid (PUFA), inhibits tumorigenesis in both androgen-dependent (LNCaP) and androgen-independent (PC-3, DU145) prostate cancer cell lines in culture. Moreover, in vivo studies with n-3 supplementation have been shown to significantly reduce PC-3 and DU145 tumor growth compared to corn oil diets rich in linoleic acid (C18:2, n-6). With evidence suggesting that n-3 PUFA dietary supplementation can inhibit tumorigenesis in CRPC, this study investigated the efficacy of DHA in combination with both abiraterone and enzalutamide in a subset of prostate tumor phenotypes in vitro. PC-3 and LNCaP cell viability were reduced with DHA in combination with either enzalutamide or abiraterone compared to primary treatments of each. These results suggest that DHA enrichment can augment abiraterone and/or enzalutamide therapy with androgen-dependent and androgen-independent prostate tumors in vitro. The results of this study provide preliminary evidence of the effectiveness of nutritional supplementation in conjunction with cancer therapeutics, and it will serve as a prelude to a pilot clinical trial evaluating the effects of nutritional supplementation with high levels of omega-3 fatty acids on enzalutamide inhibition of CRPC. Citation Format: Andrew R. Cooper, Irvin V. Ma, Andy Shao, Prem Kumar, Ronald S. Pardini. The effect of docosahexaenoic acid on androgen-dependent and androgen-independent prostate tumors in combination with abiraterone and enzalutamide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1612.