Lipids

, 44:449 | Cite as

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

Original 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.

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 

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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Copyright information

© AOCS 2009

Authors and Affiliations

  1. 1.Alberta Institute for Human Nutrition, Department of Agricultural, Food and Nutritional ScienceUniversity of AlbertaEdmontonCanada

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