Dietary polyunsaturated fatty acids modify the progression of prostate cancer

Abstract

Prostate cancer is initially characterized by androgen-dependent growth, and hormone ablation therapy typically results in regression. However, given enough time tumors invariable re-grow in the absence of androgens, an event which is often fatal. Epidemiological studies suggest PUFA may affect metastatic prostate cancer. Most animal studies investigate this disease using cell lines that are androgen-sensitive or androgen-insensitive, but few have investigated the effects of dietary PUFA on the natural progression of the disease, viz., transformation from androgen-sensitive to the hormone refractory state. We used a prostate xenograft model to examine the effects of dietary n-3 and n-6 PUFA on the growth of androgen-sensitive (CWR22) and androgen-insensitive (CWR22R) tumors, regression of CWR22 tumors following hormone ablation, and subsequent regrowth without testosterone. Dietary n-3 or n-6 PUFA did not alter rates of apoptosis/proliferation in CWR22 or CWR22R tumors. However, in comparison to dietary arachidonic acid (AA), tumors from mice fed eicosapentaenoic acid (EPA) had significantly more apoptosis and less proliferation 5 days after castration, reflecting an enhanced response to hormone ablation therapy. Furthermore, when tumor-bearing mice were maintained on AA or EPA diets for up to 6 months following castration, relapse to androgen-insensitive re-growth occurred sooner in those fed AA. These results suggest that the transition time from androgen-dependent prostate cancer to androgen-independent growth following hormone ablation therapy can be modified by the type of dietary PUFA. (Supported by DOD Prostate Cancer Research Program (MFM)).