Tolfenamic acid inhibits colon cancer cell and tumor growth and induces degradation of specificity protein (Sp) transcription factors

Satya Pathi, Xi Li, Stephen Safe

Research output: Contribution to journalArticle

26 Scopus citations

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 (50mg/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.

Original languageEnglish (US)
Pages (from-to)E53-E61
JournalMolecular Carcinogenesis
Volume53
Issue numberS1
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Colon cancer
  • Growth inhibition
  • Sp proteins
  • Tolfenamic acid

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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