Differential Ratios of Omega Fatty Acids (AA/EPA+DHA) Modulate Growth, Lipid Peroxidation and Expression of Tumor Regulatory MARBPs in Breast Cancer Cell Lines MCF7 and MDA-MB-231.
Omega 3 (n3) and Omega 6 (n6) polyunsaturated fatty acids (PUFAs) have been reported to exhibit opposing roles in cancer progression. Our objective was to determine whether different ratios of n6/n3 (AA/EPA+DHA) FAs could modulate the cell viability, lipid peroxidation, total cellular fatty acid composition and expression of tumor regulatory Matrix Attachment Region binding proteins (MARBPs) in breast cancer cell lines and in non-cancerous, MCF10A cells. Low ratios of n6/n3 (1:2.5, 1:4, 1:5, 1:10) FA decreased the viability and growth of MDA-MB-231 and MCF7 significantly compared to the non-cancerous cells (MCF10A). Contrarily, higher n6/n3 FA (2.5:1, 4:1, 5:1, 10:1) decreased the survival of both the cancerous and non-cancerous cell types. Lower ratios of n6/n3 selectively induced LPO in the breast cancer cells whereas the higher ratios induced in both cancerous and non-cancerous cell types. Interestingly, compared to higher n6/n3 FA ratios, lower ratios increased the expression of tumor suppressor MARBP, SMAR1 and decreased the expression of tumor activator Cux/CDP in both breast cancer and non-cancerous, MCF10A cells. Low n6/n3 FAs significantly increased SMAR1 expression which resulted into activation of p21WAF1/CIP1 in MDA-MB-231 and MCF7, the increase being ratio dependent in MDA-MB-231. These results suggest that increased intake of n3 fatty acids in our diet could help both in the prevention as well as management of breast cancer.
Cell and Translational Research Lab, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth University Medical College Campus, Dhankawadi, Pune, 411043, India.
Prakash P
PP
Mansara
Cell and Translational Research Lab, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth University Medical College Campus, Dhankawadi, Pune, 411043, India.
Rashmi A
RA
Deshpande
Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India.
Milind M
MM
Vaidya
Cell and Translational Research Lab, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth University Medical College Campus, Dhankawadi, Pune, 411043, India.
Ruchika
R
Kaul-Ghanekar
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000032:analysis / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000032:analysis / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015227:Lipid Peroxidation; D061986:MCF-7 Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D017962:alpha-Linolenic Acid / Q000494:pharmacology
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D036961:Matrix Attachment Region Binding Proteins; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid