Abstract 906: Decreasing omega-6 to omega-3 polyunsaturated fatty acid dietary ratios inhibit tumorigenesis in prostate cancer cells in vitro and in vivo

Abstract

Abstract Epidemiological studies have established that dietary ratios rich in omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and low in omega-6 (n-6) PUFAs correlate with lower incidences of cancer. Despite its proven efficacy, controversy has surrounded the therapeutic use of n-3 PUFAs for prostate cancer, with some studies even suggesting that they may increase its risk. Prostate cancer is the second leading cause of cancer-related deaths, and is the second most prevalent cancer among American men. Previous studies from our laboratory have shown that n-3 PUFAs, particularly docosahexaenoic acid (DHA; C22:6), initiate a wide-range of anti-tumorigenic responses in lung, breast and colon cancer. The current study examined the consequence of altering the dietary ratio of n-6:n-3 PUFAs in prostate cancer cells in vitro and in vivo, and we propose that by lowering the n-6:n-3 ratio, tumor growth will be inhibited. The antiproliferative activity of PC-3 human prostate adenocarcinoma cells was assessed in response to multiple dietary ratios of n-6 to n-3 PUFAs, using linoleic acid (LA; C18:2 n-6) and DHA at ratios of: 8:1, 4:1, 2:1, 1:1, 3:4 and 1:2, respectively. In vitro analysis revealed a dose-dependent decrease in cancer cell viability as the n-6:n-3 ratio was lowered. This suggests that the dietary ratio of n-6:n-3 PUFAs play an important role in prostate cancer cell viability. Consistent with these findings, in vivo analysis of PC-3 cells implanted into athymic nude mice displayed dose-dependent inhibition of tumor growth and final tumor weight. This may indicate an optimal dietary ratio range for prostate tumor prevention and treatment. Next, we studied the in vivo effects of diet in combination with the chemotherapeutic drug, Taxotere. Taxotere is highly lipophilic and classified as a plant alkaloid with proven effectiveness in treating a variety of cancers, including metastatic prostate cancer. After a fourteen day inoculation period, mice were distributed into groups of equal mean tumor weight and size and assigned to specific diets and treatments: high corn oil, high Menhaden oil, high DHASCO® oil, each diet in combination with Taxotere, and Taxotere alone. Surprisingly, diets rich in fat, regardless of PUFA type, enhanced the effects of Taxotere. As expected, high n-3 PUFA diets increased Taxotere efficacy and reduced tumor size three-fold compared to Taxotere alone. However, the same effect was observed in high n-6 PUFA diets as well. These findings suggest that long-chain PUFAs may increase plasma protein binding and enhance the bioavailability of Taxotere. Overall, these data demonstrate that the ratio of n-6:n-3 is important for treatment of prostate cancer, and although DHA is extremely potent as a single anti-cancer agent, combining it with other chemotherapies, like Taxotere, is an effective strategy to synergistically inhibit prostate cancer growth. Citation Format: Irvin V. Ma, Michael Mouradian, Arianne G. Sorreta, Sunggu Kang, Ronald S. Pardini. Decreasing omega-6 to omega-3 polyunsaturated fatty acid dietary ratios inhibit tumorigenesis in prostate cancer cells in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 906. doi:10.1158/1538-7445.AM2015-906