Stearidonic acid-enriched flax oil reduces the growth of human breast cancer in vitro and in vivo

• Published in: Breast cancer research and treatment Vol. 149; no. 1; pp. 17 - 29
• Main Authors: Subedi, K., Yu, H.-M., Newell, M., Weselake, R. J., Meesapyodsuk, D., Qiu, X., Shah, S., Field, C. J.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.01.2015; Springer; Springer Nature B.V
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Breast cancer; Breast Neoplasms - diet therapy; Breast Neoplasms - pathology; Cancer research; Cancer therapies; Cell Proliferation - drug effects; Cellular biology; Dietary Supplements; Fatty acids; Fatty Acids, Omega-3 - administration & dosage; Female; Genetic engineering; Genetically modified organisms; Growth; Humans; Linseed Oil - administration & dosage; Lipids; MCF-7 Cells; Medicine; Medicine & Public Health; Mice; Omega-3 fatty acids; Oncology; Preclinical Study; Rodents; Unsaturated fatty acids; Polyunsaturated fatty acid; Phospholipids; Mammary tumor; MCF-7; MDA-MB-231; MCF-12A
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-014-3212-3

The 20 and 22 carbon n-3 long-chain polyunsaturated fatty acids (LCPUFA) inhibit the growth of tumors in vitro and in animal models, but less is known about the 18 carbon n-3, stearidonic acid (SDA). This study aimed to establish and determine a mechanism for the anti-cancer activity of SDA-enriched oil (SO). SO (26 % of lipid) was produced by genetically engineering flax and used to treat human tumorigenic (MDA-MB-231, MCF-7) and non-tumorigenic (MCF-12A) breast cells. Nu / nu mice bearing MDA-MB-231 tumor were fed SO (SDA, 4 % of fat). Cell/tumor growth, phospholipid (PL) composition, apoptosis, CD95, and pro-apoptotic molecules were determined in SO-treated cells/tumors. Compared to a control lipid mixture, SO reduced ( p   <  0.05) the number of tumorigenic, but not MCF-12A cells, and resulted in higher concentration of most of the n-3 fatty acids in PL of all cells ( p   <  0.05). However, docosapentaenoic acid increased only in tumorigenic cells ( p   <  0.05). SO diet decreased tumor growth and resulted in more n-3 LCPUFA, including DPA and less arachidonic acid (AA) levels in major tumor PL ( p   <  0.05). Treatment of MDA-MB-231 cells/tumors with SO resulted in more apoptotic cells (in tumors) and in vivo and in vitro, more CD95+ positive cells and a higher expression of apoptotic molecules caspase-10, Bad, or Bid ( p   <  0.05). Supplementing SO alters total PL and PL classes by increasing membrane content of n-3 LCPUFA and lowering AA (in vivo), which is associated with increased CD95-mediated apoptosis, thereby suggesting a possible mechanism for reduce tumor survival.