Dietary n-3 Polyunsaturated Fatty Acids Enhance Hormone Ablation Therapy in Androgen-Dependent Prostate Cancer

Abstract

Hormone ablation therapy typically causes regression of prostate cancer and represents an important means of treating this disease, particularly after metastasis. However, hormone therapy inevitably loses its effectiveness as tumors become androgen-independent, and this conversion often leads to death because of subsequent poor responses to other forms of treatment. Because environmental factors , such as diet , have been strongly linked to prostate cancer , we examined the affects of dietary polyunsaturated fatty acids (PUFAs; at 1.5 wt%) on growth of androgen-dependent (CWR22) and androgen-independent (CWR22R) human prostatic cancer xenografts, the acute response of CWR22 tumors to ablation therapy, and their progression to androgen independence. Significant diet-induced changes in tumor n-3 or n-6 PUFA content had no affect on CWR22 or CWR22R tumors growing with or without androgen support, respectively. However, dietary changes that increased tumor eicosapentaenoic acid and linoleic acid content enhanced responses to ablation therapy, measured by cancer cell apoptosis and mitosis. In addition, relapse to androgen-independent growth (measured by renewed increases in tumor volume and serum prostate-specific antigen after ablation) positively correlated with tumor arachidonic acid content. There was no correlation between expression of 15-lipoxygenase isozymes or their products and tumor growth or responses to ablation. In conclusion, dietary n-3 PUFA may enhance the response of prostate cancer to ablation therapy and retard progression to androgen-independent growth by altering tumor PUFA content.

Androgens, diabetes and prostate cancer

“…For example, increasing the dietary n-3/n-6 PUFA ratio also increased this ratio in tumour membranes and reduced vascular endothelial growth factor expression, cell proliferation and tumour volume (Kobayashi et al 2006). Xenograft studies with androgen-dependent (CWR22) and androgen-independent (CWR22R)C human PCa cells have suggested that dietary changes that increased tumour n-3 PUFA content enhanced the response to androgen-ablative therapy (McEntee et al 2008). Treatment of PCa cell lines with the n-3 PUFA docosahexaenoic acid (DHA) reduced NF-kB activation and cell survival in response to oxidative stress, suggesting that DHA sensitises PCa cells to growth arrest through attenuation of the NF-kB survival pathway (Cavazos et al 2011).…”

ω–3 Fatty Acids, Genetic Variants in COX-2 and Prostate Cancer

“…This indicates that PUFAs may play a role in preventing progression of prostate cancer to the androgen-independent state, an end-stage of disease for which very few effective treatment options are available [30] .…”

Utility of adeno-associated viruses to target members of the TGF-<i>β</i> superfamily in prostate cancer therapy

“…The progression of the cancer from its initiation in the prostate, which often precedes dispersion as metastases to tissues such as bone, lymph, liver and brain leaves several windows of opportunity during which certain therapies can be administered. While several treatment methods have been developed targeting a multitude of aspects of tumour characteristics, acquisition of resistance is a familiar roadblock encountered by investigators, and circumventing this obstacle remains a difficult task [1].…”