Long chain omega-3 fatty acids and their oxidized metabolites are associated with reduced prostate tumor growth
Jean-François Bilodeau Prostaglandins, Leukotrienes and Essential Fatty Acids Volume 164, January 2021, 1
Highlights
• The enriched ω−3 diet did not reduce oxidative stress overall in tumors but favored ω−3 rather than ω−6 LC-PUFA derived isoprostanes.
• Neuroprostanes are significantly and specifically increased by androgen removal following castration in TRAMP-C2 tumors.
• Castration increased pro-inflammatory PGF2α and other prostaglandins including thromboxane.
• Decreased tumor growth under ω−3 diet could be attributed in part to EPA, reduced pro-angiogenic PGE2, and increased neuroprostanes and resolvins like RvD5.
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 ω-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 ω-3 or ω-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 ω-3 diet did not reduce oxidative stress overall in tumors but favored the formation of ω-3 rather than ω-6 derived isoprostanoids. We discovered that EPA and its oxidized-derivatives like F3-isoprostanes and prostaglandin (PG)F3α, were inversely correlated with tumor volume (spearman correlations and T-test, p<0.05). In contrast, F2-isoprostanes, adrenic acid, docosapentaenoic acid (DPAω-6) and PGE2 were positively correlated with tumor volume. Interestingly, F4-neuroprostanes, PGD2, PGF2α, and thromboxane were specifically increased in TRAMP-C2 tumors of castrated mice compared to those of eugonadal mice.
Discussion
Decreasing tumor growth under ω-3 diet could be attributed in part to increased levels of EPA 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.