title: Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition.
abstract: Acetylsalicylic acid (ASA), also known as aspirin, a classic, nonsteroidal, anti-inflammatory drug (NSAID), is widely used to relieve minor aches and pains and to reduce fever. Epidemiological studies and other experimental studies suggest that ASA use reduces the risk of different cancers including breast cancer (BC) and may be used as a chemopreventive agent against BC and other cancers. These studies have raised the tempting possibility that ASA could serve as a preventive medicine for BC. However, lack of in-depth knowledge of the mechanism of action of ASA reshapes the debate of risk and benefit of using ASA in prevention of BC. Our studies, using in vitro and in vivo tumor xenograft models, show a strong beneficial effect of ASA in the prevention of breast carcinogenesis. We find that ASA not only prevents breast tumor cell growth in vitro and tumor growth in nude mice xenograft model through the induction of apoptosis, but also significantly reduces the self-renewal capacity and growth of breast tumor-initiating cells (BTICs)/breast cancer stem cells (BCSCs) and delays the formation of a palpable tumor. Moreover, ASA regulates other pathophysiological events in breast carcinogenesis, such as reprogramming the mesenchymal to epithelial transition (MET) and delaying in vitro migration in BC cells. The tumor growth-inhibitory and reprogramming roles of ASA could be mediated through inhibition of TGF-β/SMAD4 signaling pathway that is associated with growth, motility, invasion, and metastasis in advanced BCs. Collectively, ASA has a therapeutic or preventive potential by attacking possible target such as TGF-β in breast carcinogenesis.
authors: 1] Cancer Research Unit, VA Medical Center, Kansas City, MO, USA [2] Department of Pathology, University of Kansas Medical Center, Kansas City, KS, USA.
authors: Gargi
authors: G
authors: Maity
authors: Cancer Research Unit, VA Medical Center, Kansas City, MO, USA.
authors: Archana
authors: A
authors: De
authors: 1] Cancer Research Unit, VA Medical Center, Kansas City, MO, USA [2] Department of Pathology, University of Kansas Medical Center, Kansas City, KS, USA.
authors: Amlan
authors: A
authors: Das
authors: 1] Cancer Research Unit, VA Medical Center, Kansas City, MO, USA [2] Division of Hematology and Oncology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
authors: Snigdha
authors: S
authors: Banerjee
authors: 1] Cancer Research Unit, VA Medical Center, Kansas City, MO, USA [2] Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA.
authors: Sandipto
authors: S
authors: Sarkar
authors: 1] Cancer Research Unit, VA Medical Center, Kansas City, MO, USA [2] Department of Pathology, University of Kansas Medical Center, Kansas City, KS, USA [3] Division of Hematology and Oncology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA [4] Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA.
authors: Sushanta K
authors: SK
authors: Banerjee
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008819:Mice, Nude; D016212:Transforming Growth Factor beta / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016212:Transforming Growth Factor beta; D001241:Aspirin