The role of the tissue omega-6/omega-3 fatty acid ratio in regulating tumor angiogenesis

Abstract

Angiogenesis is a necessary step in tumor growth and metastasis. It is well established that the metabolites of omega-6 and omega-3 fatty acids, which must be obtained through the diet and cannot be synthesized de novo in mammals, have differential effects on cellular processes. Omega-6 fatty acid (n-6 FA)-derived metabolites promote angiogenesis by increasing growth factor expression whereas omega-3 fatty acids (n-3 FA) have anti-angiogenic and antitumor properties. However, most studies thus far have failed to account for the role of the n-6 FA/n-3 FA ratio in angiogenesis and instead examined the absolute levels of n-6 and n-3 FA. This review highlights the biochemical interactions between n-6 and n-3 FA and focuses on how the n-6/n-3 FA ratio in tissues modulates tumor angiogenesis. We suggest that future work should consider the n-6/n-3 FA ratio to be a key element in experimental design and analysis. Furthermore, we recommend that clinical interventions should aim to both reduce n-6 metabolites and simultaneously increase n-3 FA intake.

Maternal dietary omega-3 fatty acids and placental function

“…This is supported by several in vitro studies, where n-3 PUFA administration has been shown to reduce formation of capillary-like structures (tubes) in a number of endothelial cell models (reviewed in Massaro et al (2008)). In vivo evidence is currently limited to tumor-associated angiogenesis, whereby n-3 PUFA administration limits angiogenesis via reduced synthesis of pro-angiogenic AA-derived eicosanoids and transcriptional downregulation of several growth factors (for review see Kang & Lui (2013)). In the placenta, however, n-3 PUFAs appear to promote rather than inhibit vascular development.…”

Cytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization

“…The ω-3 LCPUFAs have antithrombotic, antiangiogenic, and anti-inflammatory properties, and they compete with ω-6 LCPUFAs as substrates for synthesis of downstream metabolites by CYP enzymes, cyclooxygenases (COX), and lipoxygenases (LOX) (6,(13)(14)(15). Moreover, dietary enrichment with ω-3 LCPUFAs has been shown to protect against pathological angiogenesis-associated cancer and retinopathy (2,(16)(17)(18)(19). Of the three main pathways (COX, LOX, and CYP) involved in eicosanoid biosynthesis, the lipid mediators derived from the CYP branch are the most susceptible to changes in dietary fatty acid composition (20)(21)(22)(23).…”

“…The ω-3 double bond that distinguishes DHA and EPA from their ω-6 counterparts provides a preferred epoxidation site for specific CYP family members (20,22). In fact, most CYP isoforms can metabolize EPA and DHA with significantly higher catalytic efficiency than AA, making them uniquely susceptible to variations in the availability of these lipids (19)(20)(21)(22). CYP epoxygenases target the ω-3 double bond, resulting in an accumulation of 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) derived from EPA and 19,20-epoxydocosapentaenoic acid (19,20-…”

Applications of Nutrigenomics in Animal Sectors: A Review

“…Nicastro et al (2012) stated that mutation in Fok1 (polymorphic form of VDR) can cause colorectal cancer. Several authors have reported the importance of PUFA in disease treatment such as angiogenesis related gene expression (VEGF, MMP-2, PDGF) and cell proliferation related gene (PTEN, cyclin, p53, Wnt) that can modulate tumorigenesis (Schmitz and Ecker, 2008;Kang and Liu, 2013). In an investigation, Almendro and Gascon (2012) reported that several minerals have potential role in cancer development.…”