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.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Liu X,Abdelrahim M,Abudayyeh A,Lei P,Safe Sdoi
10.1158/1535-7163.MCT-08-1097subject
Has Abstractpub_date
2009-05-01 00:00:00pages
1207-17issue
5eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-08-1097journal_volume
8pub_type
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