Abstract
Introduction: Cancer has been associated with increased oxidative stress and deregulation of bioactiveoxylipins derived from long-chain polyunsaturated fatty acids (LC-PUFA) like arachidonic acid (AA).There is a debate whether -3 LC-PUFA could promote or prevent prostate tumor growth throughimmune modulation and reduction of oxidative stress. Our aim was to study the association betweenenzymatically or non-enzymatically produced oxidized-LC-PUFA metabolites and tumor growth in animmune-competent eugonadal and castrated C57BL/6 male mice injected with TRAMP-C2 prostatetumor cells, fed with -3 or -6 LC-PUFA-rich diets.Materials and methods: Tumor fatty acids were profiled by gas chromatography and 26 metabolitesderived from either AA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were assessedby liquid chromatography-mass spectrometry.Results: The enriched -3 diet did not reduce oxidative stress overall in tumors but favored the formationof -3 rather than -6 derived isoprostanoids. We discovered that EPA and its oxidized-derivatives likeF3-isoprostanes and prostaglandin (PG)F3, were inversely correlated with tumor volume (spearmancorrelations and T-test, p<0.05). In contrast, F2-isoprostanes, adrenic acid, docosapentaenoic acid (DPA-6) and PGE2 were positively correlated with tumor volume. Interestingly, F4-neuroprostanes, PGD2,PGF2, and thromboxane were specifically increased in TRAMP-C2 tumors of castrated mice comparedto those of eugonadal mice.Discussion: Decreasing tumor growth under -3 diet could be attributed in part to increased levels ofEPA and its oxidized-derivatives, a reduced level of pro-angiogenic PGE2 and increased levels of F4-neuroprostanes and resolvins content in tumors, suspected of having anti-proliferative and anti-inflammatory effects