Equimolar mixture of c9,t11 and t9,t11 CLA inhibits the growth and induces apoptosis in Caco-2 cells

In 2008, CLAs received a no-objection letter from the FDA on its generally recognized as safe (GRAS) status for certain foods. However, aside from the mixture of c9, t11-CLA and t10, c12-CLA, other CLA mixtures are still not used in food production. The effects of different concentrations (25, 50, 100, and 200 µmol/L) of CLA mixture (c9, t11-CLA and t9, t11-CLA) on the human colorectal carcinoma cell line Caco-2 cells after various treatment times (1, 2, 3, and 4 days) and the induced apoptosis were examined in the study. The mRNA expression level and activities of caspase-3, -8, and -9 were determined via quantitative real-time PCR and caspase-3, -8, and -9 assay kits. The results indicated that the CLA mixture inhibited the proliferation of the Caco-2 cells, and the antiproliferative effects were closely related to treatment time and concentration. Meanwhile, the CLA mixture increased the mRNA expression level and activities of caspase-3, -8, and -9 compared with control which suggested apoptosis induced by CLA mixture was related to the caspase pathway. In conclusion, the CLA mixture can inhibit Caco-2 cell proliferation and induce its apoptosis through increasing caspase 3, 8, and 9 expression and activities. Practical applications: In the food industry, lactic acid bacteria (LAB) are generally recognized as safe and important for the production of fermented food and may be used as probiotic bacteria in the human gastrointestinal tract, contributing to pathogen inhibition and immunomodulation. C9, t11-CLA and t9, t11-CLA isomers used for the present study were obtained from the conversion of linoleic acid by Lactobacillus helveticus L7 (used as a probiotic bacterial in our laboratory). Here, the mixture of c9, t11-CLA and t9, t11-CLA had a synergistic antiproliferation effect on the Caco-2 cells which suggested that the CLA mixture has potential health value, and can be a beneficial supplement in the food industry.

[1]  M. Belury,et al.  c9t11-Conjugated linoleic acid-rich oil fails to attenuate wasting in colon-26 tumor-induced late-stage cancer cachexia in male CD2F1 mice. , 2011, Molecular nutrition & food research.

[2]  W. Bielecki,et al.  Influence of diet enriched with conjugated linoleic acids on their distribution in tissues of rats with DMBA induced tumors , 2010, Lipids in Health and Disease.

[3]  J. Rosa,et al.  Conjugated Linoleic Acid: good or bad nutrient , 2010, Diabetology & metabolic syndrome.

[4]  F. Cecconi,et al.  Neuronal caspase-3 signaling: not only cell death , 2010, Cell Death and Differentiation.

[5]  H. Roche,et al.  Conjugated linoleic acid and inflammatory cell signalling. , 2010, Prostaglandins, leukotrienes, and essential fatty acids.

[6]  P. Opanasopit,et al.  In vitro Permeability Enhancement in Intestinal Epithelial Cells (Caco-2) Monolayer of Water Soluble Quaternary Ammonium Chitosan Derivatives , 2010, AAPS PharmSciTech.

[7]  T. Yanagita,et al.  Conjugated linoleic acid suppresses colon carcinogenesis in azoxymethane-pretreated rats with long-term feeding of diet containing beef tallow , 2010, Journal of Gastroenterology.

[8]  E. Siebelink,et al.  Effect of a High Intake of Conjugated Linoleic Acid on Lipoprotein Levels in Healthy Human Subjects , 2010, PloS one.

[9]  Yeonhwa Park.  Conjugated linoleic acid (CLA): Good or bad trans fat? , 2009 .

[10]  H. Cho,et al.  trans-10,cis-12 Conjugated linoleic acid induces depolarization of mitochondrial membranes in HT-29 human colon cancer cells: a possible mechanism for induction of apoptosis. , 2009, Journal of medicinal food.

[11]  S. Toubro,et al.  Conjugated linoleic acids reduce body fat in healthy postmenopausal women. , 2009, The Journal of nutrition.

[12]  C. Field,et al.  Conjugated Linoleic Acid Decreases MCF-7 Human Breast Cancer Cell Growth and Insulin-Like Growth Factor-1 Receptor Levels , 2009, Lipids.

[13]  P. Yan,et al.  Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue , 2008, BMC Cancer.

[14]  J. Prates,et al.  Diet supplementation with the cis-9,trans-11 conjugated linoleic acid isomer affects the size of adipocytes in Wistar rats. , 2008, Nutrition research.

[15]  M. Q. Kemp,et al.  Cyclooxygenase-2 Promoter Activation by the Aromatic Hydrocarbon Receptor in Breast Cancer MCF-7 Cells: Repressive Effects of Conjugated Linoleic Acid , 2007, Nutrition and cancer.

[16]  S. Monereo,et al.  Conjugated linoleic acid (CLA) and obesity , 2007, Public Health Nutrition.

[17]  C. Bocca,et al.  Antiproliferative effect of conjugated linoleic acid in caco-2 cells: Involvement of PPARγ and APC/β-catenin pathways , 2007 .

[18]  B. Lisafeld,et al.  Conjugated linoleic acid induces apoptosis of murine mammary tumor cells via Bcl-2 loss. , 2007, Biochemical and biophysical research communications.

[19]  G. Fernandes,et al.  Biological effects of conjugated linoleic acids in health and disease. , 2006, The Journal of nutritional biochemistry.

[20]  Takuji Tanaka,et al.  Potent inhibitory effect of trans9, trans11 isomer of conjugated linoleic acid on the growth of human colon cancer cells. , 2006, The Journal of nutritional biochemistry.

[21]  Shafiqur Rahman,et al.  Intestinal Bifidobacteria That Produce trans-9, trans-11 Conjugated Linoleic Acid: A Fatty Acid With Antiproliferative Activity Against Human Colon SW480 and HT-29 Cancer Cells , 2006, Nutrition and cancer.

[22]  S. Kishino,et al.  Production of conjugated fatty acids by lactic acid bacteria. , 2005, Journal of bioscience and bioengineering.

[23]  M. Kern,et al.  Effects of conjugated linoleic acid supplementation on blood lipids and adiposity of rats fed diets rich in saturated versus unsaturated fat. , 2005, Pharmacological research.

[24]  R. Nicolosi,et al.  Conjugated linoleic acid isomer effects in atherosclerosis: Growth and regression of lesions , 2004, Lipids.

[25]  E. Kim,et al.  Conjugated linoleic acid (CLA) inhibits growth of Caco-2 colon cancer cells: possible mediation by oleamide. , 2002, Anticancer research.

[26]  S. Kishino,et al.  Conjugated linoleic acid production from linoleic acid by lactic acid bacteria , 2002 .

[27]  T. Miyazawa,et al.  The growth inhibitory effect of conjugated linoleic acid on a human hepatoma cell line, HepG2, is induced by a change in fatty acid metabolism, but not the facilitation of lipid peroxidation in the cells. , 2001, Biochimica et biophysica acta.

[28]  Yu-sheng Cao,et al.  Antiproliferative effects of conjugated linoleic acid on human colon adenocarcinoma cell line Caco-2. , 2007, Asia Pacific journal of clinical nutrition.