docosapentaenoic-acid and Breast-Neoplasms

Vitamin C (Vit C) is an important physiological antioxidant with growing applications in cancer. Somatostatin (SST) is a natural peptide with growth inhibitory effect in several mammary cancer models.. The combined effects of SST and Vit C supplementation have never been studied in breast cancer cells so far.. We used MCF-7 and MDA-MB231 breast cancer cells incubated with SST for 24h, in the absence and presence of Vit C, at their EC50 concentrations, to evaluate membrane fatty acid-profiles together with the follow-up of EGFR and MAPK signaling pathways.. The two cell lines gave different membrane reorganization: in MCF-7 cells, decrease of omega-6 linoleic acid and increase of omega-3 fatty acids (Fas) occurred after SST and SST+Vit C incubations, the latter also showing significant increases in MUFA, docosapentaenoic acid and mono-trans arachidonic acid levels. In MDA-MB231 cells, SST+Vit C incubation induced significant membrane remodeling with an increase of stearic acid and mono-trans-linoleic acid isomer, diminution of omega-6 linoleic, arachidonic acid and omega-3 (docosapentaenoic and docosadienoic acids). Distinct signaling pathways in these cell lines were studied: in MCF-7 cells, incubations with SST and Vit C, alone or in combination significantly decreased EGFR and MAPK signaling, whereas in MDA-MB231 cells, SST and Vit C incubations, alone or combined, decreased p- P44/42 MAPK levels, and increased EGFR levels.. Our results showed that SST and Vit C can be combined to induce membrane fatty acid changes, including lipid isomerization through a specific free radical-driven process, influencing signaling pathways.

Topics: Arachidonic Acids; Ascorbic Acid; Breast Neoplasms; Cell Extracts; Cell Line, Tumor; Cell Membrane; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Green Fluorescent Proteins; Humans; Lipids; Mitogen-Activated Protein Kinase Kinases; Phospholipids; Signal Transduction; Somatostatin; Stearic Acids

This study prospectively investigates associations between fatty acids assessed in plasma phospholipids (PPL) and diet, and breast cancer risk, including subgroups defined by hormone receptor status.. We performed a case-cohort analysis within the Melbourne Collaborative Cohort Study using a random sample of 2,021 women and 470 breast cancer cases. At baseline, fatty acids were assessed in PPL and estimated from diet using a 121-item food frequency questionnaire. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using Cox regression.. Breast cancer risk was positively associated with %PPL saturated fatty acids (SFA); HRQ5vsQ1 = 1.64 (95 % CI 1.17-2.30); p trend = 0.004. Positive associations were found for ER+ or PR+ tumors for %PPL SFA and palmitic acid and for ER-/PR- tumors for %PPL n-6 polyunsaturated fatty acid (PUFA), TFA, TFA 16:1, and TFA 18:1n-7 (all p homogeneity <0.05). Breast cancer risk was inversely associated with dietary docosapentaenoic acid (DPA); HRQ5vsQ1 = 0.57 (95 % CI 0.40-0.82); p trend = 0.001 [with similar inverse associations observed for dietary docosahexaenoic (DHA) and eicosapentaenoic acid (EPA)] and positively associated with dietary n-6:n-3 PUFA. Inverse associations for ER-/PR- tumors were found for dietary dihomo-γ-linolenic acid (DGLA) for older women (p homogeneity = 0.04).. Breast cancer risk was positively associated with %PPL SFA and the ratio of dietary n-6 to n-3 PUFA and inversely associated with dietary long-chain n-3 PUFA intake. Some associations between fatty acids and breast cancer varied by age and tumor phenotype defined by hormone receptor status. Increased intake of fish and other foods rich in long-chain n-3 PUFAs and reduced n-6 PUFA intake might reduce breast cancer risk.

Topics: 8,11,14-Eicosatrienoic Acid; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Animals; Breast Neoplasms; Case-Control Studies; Diet; Dietary Fats; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Fishes; Humans; Middle Aged; Phospholipids; Proportional Hazards Models; Prospective Studies; Receptors, Estrogen; Receptors, Progesterone; Risk

Natural product drug discovery efforts frequently utilize noncellular screening assays. Fatty acids are commonly found in natural product extracts, and some have been shown to interfere with noncellular assays. Several pure fatty acids were tested using a noncellular aromatase assay, with the unsaturated analogues showing strong inhibitory activity, while the saturated analogues were inactive. Unsaturated fatty acids were further tested against SK-BR-3 hormone-independent human breast cancer cells that overexpress aromatase and were found to be inactive. In natural product screening efforts, especially using plant seeds, it is recommended that extracts active in noncellular bioassays should be dereplicated for the presence of fatty acids prior to bioassay-guided fractionation.

Topics: Aromatase; Biological Products; Breast Neoplasms; Fatty Acids; Female; Humans; Microsomes; Placenta; Tumor Cells, Cultured