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Mol Cancer Ther. 2009 May 12. [Epub ahead of print]

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

Liu X, Abdelrahim M, Abudayyeh A, Lei P, Safe S.
Departments of 1Biochemistry and Biophysics and 2Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas; 3Cancer Research Institute, M. D. Anderson Cancer Center, Orlando Regional Health, Care, Orlando, Florida; and 4Department of Internal Medicine, Baylor College of Medicine, One Baylor Plaza and 5Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas.
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. [Mol Cancer Ther 2009;8(5):1207-17].
PMID: 19435870