Long chain omega-3 fatty acids and their oxidized metabolites are associated with reduced prostate tumor growth

Introduction: Cancer has been associated with increased oxidative stress and deregulation of bioactive oxylipins derived from long-chain polyunsaturated fatty acids (LC-PUFA) like arachidonic acid (AA). There is a debate whether omega-3 LC-PUFA could promote or prevent prostate tumor growth through immune modulation and reduction of oxidative stress. Our aim was to study the association between enzymatically or non-enzymatically produced oxidized-LC-PUFA metabolites and tumor growth in an immune-competent eugonadal and castrated C57BL/6 male mice injected with TRAMP-C2 prostate tumor cells, fed with omega-3 or omega-6 LC-PUFA-rich diets. Materials and methods: Tumor fatty acids were profiled by gas chromatography and 26 metabolites derived from either AA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were assessed by liquid chromatography-mass spectrometry. Results: The enriched omega-3 diet did not reduce oxidative stress overall in tumors but favored the formation of omega-3 rather than omega-6 derived isoprostanoids. We discovered that EPA and its oxidized-derivatives like F-3-isoprostanes and prostaglandin (PG)F-3 alpha, were inversely correlated with tumor volume (spearman correlations and T-test, p<0.05). In contrast, F-2-isoprostanes, adrenic acid, docosapentaenoic acid (DPA(omega-6)) and PGE(2) were positively correlated with tumor volume. Interestingly, F-4-neuroprostanes, PGD(2), PGF(2 alpha), and thromboxane were specifically increased in TRAMP-C2 tumors of castrated mice compared to those of eugonadal mice. Discussion: Decreasing tumor growth under omega-3 diet could be attributed in part to increased levels of EPA and its oxidized-derivatives, a reduced level of pro-angiogenic PGE(2) and increased levels of F-4-neuroprostanes and resolvins content in tumors, suspected of having anti-proliferative and anti-inflammatory effects.

Automated summary

This study found that a diet rich in omega-3 may help reduce prostate tumor growth in mice, potentially through the effects of EPA and its oxidized derivatives on tumor growth.