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

Abstract
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.
AuthorsK Subedi, H-M Yu, M Newell, R J Weselake, D Meesapyodsuk, X Qiu, S Shah, C J Field
JournalBreast cancer research and treatment (Breast Cancer Res Treat) Vol. 149 Issue 1 Pg. 17-29 (Jan 2015) ISSN: 1573-7217 [Electronic] Netherlands
PMID25417173 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Fatty Acids, Omega-3
  • Linseed Oil
  • stearidonic acid
Topics
  • Animals
  • Apoptosis (drug effects)
  • Breast Neoplasms (diet therapy, pathology)
  • Cell Proliferation (drug effects)
  • Dietary Supplements
  • Fatty Acids, Omega-3 (administration & dosage)
  • Female
  • Humans
  • Linseed Oil (administration & dosage)
  • MCF-7 Cells
  • Mice

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