title: 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.
authors.affiliation: Division of Nutrition, 4-126A Li Ka Shing Center for Health Research Innovation, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Subedi
authors.forename: H-M
authors.initials: HM
authors.lastname: Yu
authors.forename: M
authors.initials: M
authors.lastname: Newell
authors.forename: R J
authors.initials: RJ
authors.lastname: Weselake
authors.forename: D
authors.initials: D
authors.lastname: Meesapyodsuk
authors.forename: X
authors.initials: X
authors.lastname: Qiu
authors.forename: S
authors.initials: S
authors.lastname: Shah
authors.forename: C J
authors.initials: CJ
authors.lastname: Field
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000178:diet therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008043:Linseed Oil / Q000008:administration & dosage*; D061986:MCF-7 Cells; D051379:Mice
chemical_list: D015525:Fatty Acids, Omega-3; D008043:Linseed Oil; C062895:stearidonic acid