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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.

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Abbreviations

AA:

Arachidonic acid

ALA:

α-linolenic acid

CD95:

Fas ligand death receptor

DGLA:

Dihomo γ-linolenic acid

DHA:

Docosahexaenoic acid

DPA:

Docosapentaenoic acid

EPA:

Eicosapentaenoic acid

ETA:

Eicosatetraenoic acid

GC:

Gas chromatography

GLA:

γ-linolenic acid

LA:

Linoleic acid

LCPUFA:

Long-chain polyunsaturated fatty acid

OA:

Oleic acid

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PI:

Phosphatidylinositol

PL:

Phospholipid

PS:

Phosphatidylserine

SDA:

Stearidonic acid

SO:

SDA-enriched oil

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Acknowledgments

The authors acknowledge the technical support of Susan Goruk, Chris Kazala, and Robin Miles. Funding for this project came in part from the Canadian Institute of Health Sciences (CIHR) and in part from an investigator initiated grant to a provincial government agency Alberta Innovates Biosolutions (AIBS) that administered the funds to this project from their funding partner, the Alberta Canola Producers (ACP). RJW is grateful for the support provided by the Canada Research Chairs Program.

Conflicts of interest

The authors have no financial association with the owner of the patent or the funders of this project.

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Correspondence to C. J. Field.

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Subedi, K., Yu, HM., Newell, M. et al. Stearidonic acid-enriched flax oil reduces the growth of human breast cancer in vitro and in vivo. Breast Cancer Res Treat 149, 17–29 (2015). https://doi.org/10.1007/s10549-014-3212-3

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Keywords

  • MDA-MB-231
  • MCF-7
  • MCF-12A
  • Mammary tumor
  • Polyunsaturated fatty acid
  • Phospholipids