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Conjugated Linoleic Acid Decreases MCF-7 Human Breast Cancer Cell Growth and Insulin-Like Growth Factor-1 Receptor Levels

Lipids volume 44, pages 449–458 (2009)Cite this article

Abstract

In vitro work suggests that conjugated linoleic acid (CLA) isomers (c9,t11 and t10,c12) are cytotoxic to human breast cancer cells, however the mechanism remains unknown. Using human MCF-7 breast cancer cells, we examined the effects of c9,t11 and t10,c12 CLA compared to oleic acid (OA), linoleic acid (LA), or untreated cells on cell membrane phospholipid composition, cell survival, and the insulin-like growth factor-I (IGF-I) and the downstream insulin receptor substrate-1 (IRS-1). Both CLA isomers were incorporated into membrane phospholipids (p < 0.05). Compared to untreated cells, c9,t11 or t10,c12 CLA significantly reduced the metabolic activity of IGF-I stimulated MCF-7 cells, increased lactate dehydrogenase (LDH) release, and decreased cellular concentrations of the IGF-I receptor (IGF-IR) and insulin receptor substrate-1 (p < 0.05). Incubation with t10,c12 CLA also reduced the levels of phosphorylated IGF-1R. The effects on all of these measures were greater (p < 0.05) for t10,c12 CLA compared to c9,t11 CLA. There were few differences between LA-treated and c9,t11 CLA-treated cells, whereas cellular metabolic activity, LDH release, and IGF-IR concentrations differed between t10,c12 CLA-treated and LA-treated cells (p < 0.05). OA stimulated growth compared to the untreated condition (p < 0.05). In summary, this study demonstrated that the t10,c12 CLA isomer inhibits growth of MCF-7 cells and suggested that this may be mediated through incorporation into cellular phospholipids and interference with the function of IGF-I and related signaling proteins.

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Abbreviations

AA:

Arachidonic acid

BSA:

Bovine serum albumin

c9, t11 CLA:

Cis-9, trans-11 CLA

CLA:

Conjugated linoleic acid

DHA:

Docosahexaenoic acid

DMEM:

Dulbecco’s modified Eagle medium

FBS:

Fetal bovine serum

IGF-I:

Insulin-like growth factor I

IGF-IR:

Insulin-like growth factor-I receptor

IRS-1:

Insulin receptor substrate-1

LA:

Linoleic acid

LDH:

Lactate dehydrogenase

MUFA:

Monounsaturated fatty acids

OA:

Oleic Acid

PUFA:

Polyunsaturated fatty acid

SFA:

Saturated fatty acids

t10,c12 CLA:

trans-10, cis-12 CLA

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Acknowledgments

The authors would like to acknowledge the help of Patricia Biondo in putting together this manuscript and the technical assistance of Marnie Newell, Paige Sorochan and Susan Goruk. D. Amarù was the recipient of a post-graduate studentship from the Natural Sciences and Engineering Research Council of Canada. Funding for this study came from the CLA network through a grant from the Alberta Agriculture Research Funding Consortium.

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Authors and Affiliations

  1. Alberta Institute for Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, 4-126A HRIF East, Edmonton, AB, T6G 2P5, Canada

    Danielle L. Amarù & Catherine J. Field

Authors
  1. Danielle L. Amarù
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  2. Catherine J. Field
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Correspondence to Catherine J. Field.

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Amarù, D.L., Field, C.J. Conjugated Linoleic Acid Decreases MCF-7 Human Breast Cancer Cell Growth and Insulin-Like Growth Factor-1 Receptor Levels. Lipids 44, 449–458 (2009). https://doi.org/10.1007/s11745-009-3288-4

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  • DOI: https://doi.org/10.1007/s11745-009-3288-4

Keywords

  • c9,t11 CLA
  • t10,c12 CLA
  • Breast cancer
  • Conjugated linoleic acid
  • Insulin-like growth factor-I
  • IGF-I receptor
  • Insulin receptor substrate-1
  • Mammary
  • MCF-7
  • Tumour