title: Tolfenamic acid inhibits colon cancer cell and tumor growth and induces degradation of specificity protein (Sp) transcription factors.
abstract: Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug (NSAID) that inhibits lung, esophageal, breast and pancreatic cancer cell and tumor growth, and this study investigated the anticancer activity of TA in colon cancer. TA inhibited growth and induced apoptosis in RKO, SW480, HT-29, and HCT-116 colon cancer cells, and TA (50 mg/kg/d) also inhibited tumor growth in athymic nude mice bearing RKO cells as xenografts. TA downregulated expression of Sp proteins (Sp1, Sp3, and Sp4) in colon cancer cells and this was accompanied by decreased expression of several Sp-regulated growth promoting (cyclin D1, hepatocyte growth factor receptor), angiogenic (vascular endothelial growth factor (VEGF) and its receptor 1), survival (survivin and bcl-2), and inflammatory (NFκBp65/p50) gene products. The mechanism of TA-mediated effects on Sp proteins was due to activation of caspases. These results now extend the number of NSAIDs that may have clinical potential for colon cancer chemotherapy and show that the anticancer activity of TA is due, in part, to targeting Sp transcription factors.
authors.affiliation: Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas.
authors.forename: Satya
authors.initials: S
authors.lastname: Pathi
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Stephen
authors.initials: S
authors.lastname: Safe
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D051703:Sp Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D062367:ortho-Aminobenzoates / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051703:Sp Transcription Factors; D062367:ortho-Aminobenzoates; C009500:tolfenamic acid
keywords: Sp proteins; colon cancer; growth inhibition; tolfenamic acid