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.
Highlights
Cancer is defined as a group of neoplastic cells that grow uncontrollably and destroy the body’s healthy physiology
Proinflammatory cytokine, adipokine, and angiogenesis-related mediators were analyzed in supernatants of 3T3-L1 adipocytes to evaluate the chemopreventive properties of aspirin, as shown in Figure 1. 3T3-L1 cells, in which inflammation was induced by TNF-α and lipopolysaccharide (LPS) stimulation, were treated with various doses of aspirin for 24 h
In the aspirin-treated TNF-α model of 3T3-L1 cells, significant decreases were observed in interleukin-6 (IL-6), IL-1β, macrophage chemoattractant
Summary
Cancer is defined as a group of neoplastic cells that grow uncontrollably and destroy the body’s healthy physiology. Breast cancer is one of the most frequent and ubiquitous cancers throughout every region of the world. In 2018, World Health Organization (WHO) statistics indicated that breast cancer affects 2.1 million women every year and encompasses approximately 15% of all cancer-related mortality amongst women [1]. Epidemiological evidence shows that 30–50% of all cancers are preventable, mainly through changes in lifestyle, environment, and diet [1]. Prevention is considered to be the most effective and economically advantageous strategy in controlling several diseases, especially cancer [1]. In 2016, the WHO estimated that over 650 million adults worldwide were overweight or obese, comprising approximately 39% and 13% of the global population, respectively [2]. In the adipose tissue microenvironment, several types of immune cells demonstrate increased infiltration into adipose tissue, setting off a series of proinflammatory cytokine secretions, for example, interleukin-6 (IL-6), leptin, and tumor necrosis factor-alpha (TNF-α) [3]
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