1. Aspirin Modifies Inflammatory Mediators and Metabolomic Profiles and Contributes to the Suppression of Obesity-Associated Breast Cancer Cell Growth.
- Author
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Hsieh CC, Chiu HH, Wang CH, and Kuo CH
- Subjects
- 3T3-L1 Cells, Adipocytes metabolism, Adipose Tissue metabolism, Animals, Aspirin metabolism, Breast pathology, Cell Differentiation drug effects, Chemokine CCL2 metabolism, Coculture Techniques, Culture Media, Conditioned pharmacology, Female, Inflammation drug therapy, Inflammation pathology, Inflammation Mediators metabolism, Interleukin-1beta metabolism, Interleukin-6 metabolism, Macrophages metabolism, Metabolomics, Mice, Obesity metabolism, Plasminogen Activator Inhibitor 1 metabolism, Tumor Necrosis Factor-alpha metabolism, Aspirin pharmacology, Breast Neoplasms drug therapy, Cell Proliferation drug effects
- Abstract
Breast cancer is the most common cancer among women. Adiposity generally accompanies immune cell infiltration and cytokine secretion, which is ideal for tumor development. Aspirin is a chemopreventive agent against several types of cancer. The aim of this study was to investigate whether aspirin inhibits the growth of 4T1 breast cancer cells by inhibiting the inflammatory response and regulating the metabolomic profile of 3T3-L1 adipocytes. 3T3-L1 adipocyte-conditioned medium (Ad-CM) was used to mimic the obese adipose tissue microenvironment in 4T1 cells. The results revealed that aspirin inhibited macrophage chemoattractant protein (MCP-1), interleukin (IL-6), IL-1β, and plasminogen activator inhibitor (PAI-1) production in 3T3-L1 adipocytes stimulated by tumor necrosis factor-alpha (TNF-α) and lipopolysaccharide (LPS). In the obesity-associated model, Ad-CM significantly promoted 4T1 cell growth and migration, which were attenuated after aspirin treatment. The results of metabolic analyses using Ad-CM showed that amino acid metabolites and oxidative stress were increased in mature 3T3-L1 adipocytes compared to those in fibroblasts. Aspirin treatment modified metabolites involved in suppressing lipogenesis, oxidative stress, and neoplastic formation. In the relative fatty acid quantitation analysis of Ad-CM, aspirin diminished fatty acid contents of C16:1, C18:1, C18:2, C20:4, and C24:1. This study is the first to show that aspirin modifies the metabolomics and fatty acid composition of 3T3-L1 adipocytes and inhibits obesity-associated inflammation that contributes to obesity-related breast cancer cell growth and migration.
- Published
- 2020
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