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.