The nonsteroidal anti-inflammatory drug tolfenamic acid inhibits BT474 and SKBR3 breast cancer cell and tumor growth by repressing erbB2 expression

Xinyi Liu, Maen Abdelrahim, Ala Abudayyeh, Ping Lei, Stephen Safe

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Tolfenamic acid (TA) is a nonsteroidal anti-inflammatory drug that inhibits pancreatic cancer cell and tumor growth through decreasing expression of specificity protein (Sp) transcription factors. TA also inhibits growth of erbB2-overexpressing BT474 and SKBR3 breast cancer cells; however, in contrast to pancreatic cancer cells, TA induced down-regulation of erbB2 but not Sp proteins. TA-induced erbB2 down-regulation was accompanied by decreased erbB2-dependent kinase activities, induction of p27, and decreased expression of cyclin D1. TA also decreased erbB2 mRNA expression and promoter activity, and this was due to decreased mRNA stability in BT474 cells and, in both cell lines, TA decreased expression of the YY1 and AP-2 transcription factors required for basal erbB2 expression. In addition, TA also inhibited tumor growth in athymic nude mice in which BT474 cells were injected into the mammary fat pad. TA represents a novel and promising new anticancer drug that targets erbB2 by decreasing transcription of this oncogene.

Original languageEnglish (US)
Pages (from-to)1207-1217
Number of pages11
JournalMolecular Cancer Therapeutics
Volume8
Issue number5
DOIs
StatePublished - May 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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