Aspirin Modifies Inflammatory Mediators and Metabolomic Profiles and Contributes to the Suppression of Obesity-Associated Breast Cancer Cell Growth

Abstract

<jats:p>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.</jats:p>

Seed-derived peptide lunasin suppressed breast cancer cell growth by regulating inflammatory mediators, aromatase, and estrogen receptors

“…Another mediator, PGE 2 , is the major derivative of cyclooxygenase (COX) catalysis and has been widely discussed as a hallmark of the link between inflammation and tumor development by promoting proliferation, invasion, metastasis, and angiogenesis ( 28 ). Accordingly, non-steroidal anti-inflammatory drugs, such as aspirin, act to inhibit PGE 2 production and have been demonstrated to inhibit tumor initiation and progression ( 29 , 30 ). It has been revealed that the overexpression of COX-2 is a prominent characteristic in all clinical stages of breast cancer patients ( 29 ).…”

Interleukin-6: Molecule in the Intersection of Cancer, Ageing and COVID-19

“…In the context of this article, it should be mentioned that these substances reduce the actual levels of IL-6 and TNF-α, factors known for their supporting role in tumour growth and spread, as discussed above [49,50]. Moreover, ASA has a direct effect on the production of IL-6 by adipocytes, and so it has an indirect effect on cancer [51]. ASA also stimulates apoptosis in cancer cells [52].…”

Pancreatic Cancer and Microenvironments: Implications of Anesthesia

“…Lv et al demonstrated that ropivacaine alleviated high-glucose-induced brain microvascular endothelial injury through the downregulation of MMPs and the attenuation of oxidative stress [ 163 ]. In breast cancer cells, aspirin-modified metabolites were involved in suppressing lipogenesis, oxidative stress, and neoplastic formation [ 164 ]. On the other hand, Kacprzak and Pawliczak reported that aspirin induced oxidative stress in cells, a condition also supported by the inflammatory milieu [ 165 ].…”