Proteomic changes induced by effective chemopreventive ratios of n-3:n-6 fatty acids and tamoxifen against MNU-induced mammary cancer in the rat.

Abstract

We used a proteomic approach to gain insights into the mechanisms of protection at the protein level by a high n-3:n-6 ratio in the absence and presence of Tamoxifen. Four groups were treated with 1-methyl-1-nitrosourea (MNU) and fed the following diets with varied n-3:n-6 ratios; group 1 = 1:1; groups 2 and 3 = 10:1 and 25:1, respectively; group 4: (25:1) plus Tamoxifen (1 mg/kg diet). The plasma from six rats/group was pooled and analyzed with the isobaric tags for relative and absolute quantitation method; 148 proteins were identified with 95% confidence by ProteinPilot 4.0. In plasma of rats fed 10:1, 25:1 n-3:n-6, and 25:1 plus Tamoxifen, the number of proteins that met our criteria (P ≤ 0.05, error factor ≤ 2) were 10, 14, and 19 proteins, respectively. Selected proteins were further validated by Western blotting. Compared to 1:1, both 10:1 and 25:1 diets upregulated vitamin D binding protein, gelsolin, and 14-3-3 sigma, reported to have tumor suppressive effects, whereas alpha-1B-glycoprotein, which has been reported to be elevated in the serum of breast cancer patients was decreased. Compared to 25:1, the 25:1 plus Tamoxifen diet downregulated apolipoprotein E, haptoglobin, and inter-α-inhibitor H4 heavy chain. Ingenuity pathway analysis determined that the trends of specific proteins were related to lipid metabolism in the 25:1 n-3:n-6 group, whereas the 25:1 n-3:n-6 plus Tamoxifen group included proteins involved in cancer and inflammation. Our results show that several proteins were altered in a manner consistent with chemoprevention. Such proteins may serve as biomarkers to monitor efficacy of n-3 and Tamoxifen in future clinical chemoprevention trials.

• Authors: Christine G Skibinski, Henry J Thompson, Arunangshu Das, Andrea Manni, James D Bortner, Anne Stanley, Bruce A Stanley, Karam El-Bayoumy
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 6 Issue 9 Pg. 979-88 (Sep 2013) ISSN: 1940-6215 [Electronic] United States
• PMID: 23880232 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkylating Agents
• Antineoplastic Agents, Hormonal
• Biomarkers, Tumor
• Fatty Acids, Omega-6
• Tamoxifen
• Methylnitrosourea

Topics

• Alkylating Agents (toxicity)
• Animals
• Antineoplastic Agents, Hormonal (pharmacology)
• Antineoplastic Combined Chemotherapy Protocols
• Biomarkers, Tumor (metabolism)
• Diet
• Fatty Acids, Omega-6 (pharmacology)
• Female
• Mammary Neoplasms, Experimental (chemically induced, drug therapy, metabolism)
• Methylnitrosourea (toxicity)
• Rats
• Rats, Sprague-Dawley
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Tamoxifen (pharmacology)