t10c12 conjugated linoleic acid suppresses HER2 protein and enhances apoptosis in SKBr3 breast cancer cells: possible role of COX2

• Published in: PloS one 2009-04, Vol.4 (4), p.e5342-e5342
• Main Authors: Flowers, Margaret, Thompson, Patricia A
• Format: Article
• Language: English
• Subjects: Acids; Angiogenesis; Annexin V; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Anticancer properties; Apoptosis; Apoptosis - drug effects; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer cells; Cancer therapies; Care and treatment; Cell Biology/Cell Signaling; Cell cycle; Cell Line, Tumor; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cytometry; Dinoprostone - metabolism; Disease resistance; Enzyme-linked immunosorbent assay; Epidermal growth factor; ErbB-2 protein; Fatty acids; Female; Flow cytometry; Gene Expression - drug effects; Genes, erbB-2; Health aspects; Humans; Immunofluorescence; Kinases; Linoleic acid; Linoleic acids; Linoleic Acids, Conjugated - pharmacology; Medical treatment; Metabolism; Metastasis; Models, Biological; Monoclonal antibodies; NF-κB protein; Nutrition; Oncology/Breast Cancer; Penicillin; Physiological aspects; Prostaglandin E2; Prostaglandins E; Protein expression; Proteins; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - genetics; Rodents; Targeted cancer therapy; Transcription Factor RelA - metabolism; Transcription factors; Transgenic animals; Trastuzumab; Treatment resistance; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-α; Tumorigenesis; Unsaturated fatty acids; Women's Health/Breast Cancer
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0005342

HER2-targeted therapy with the monoclonal antibody trastuzumab (Herceptin) has improved disease-free survival for women diagnosed with HER2-positive breast cancers; however, treatment resistance and disease progression are not uncommon. Current data suggest that resistance to treatment in HER2 cancers may be a consequence of NF-kappaB overexpression and increased COX2-derived prostaglandin E2 (PGE(2)). Conjugated linoleic acid (CLA) has been shown to have anti-tumor properties and to inhibit NF-kappaB activity and COX2. In this study, HER2-overexpressing SKBr3 breast cancer cells were treated with t10c12 CLA. Protein expression of the HER2 receptor, nuclear NF-kappaB p65, and total and phosphorylated IkappaB were examined by western blot and immunofluorescence. PGE(2) levels were determined by ELISA. Proliferation was measured by metabolism of 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and apoptosis was measured by FITC-conjugated Annexin V staining and flow cytometry. We observed a significant decrease in HER2 protein expression on western blot following treatment with 40 and 80 microM t10c12 CLA (p