Nitro-aspirin inhibits MCF-7 breast cancer cell growth: Effects on COX-2 expression and Wnt/β-catenin/TCF-4 signaling

Document Type

Journal Article

Publication Date

11-15-2009

Journal

Biochemical Pharmacology

Volume

78

Issue

10

DOI

10.1016/j.bcp.2009.06.104

Keywords

β-Catenin; Aspirin; Breast cancer; Cancer; Chemoprevention; COX-2; NO-releasing aspirin; Protein kinase C

Abstract

There is current evidence implicating the Wnt/β-catenin/TCF pathway in breast cancer. We investigated the effect of para- and meta-positional isomers of nitric oxide-releasing aspirin (NO-ASA), and aspirin (ASA) on MCF-7 human breast cancer cell growth and β-catenin/TCF signaling. The p- and m-NO-ASA isomers strongly inhibited cell growth and β-catenin/TCF transcriptional activity compared to ASA; the IC50s for growth inhibition were 57 ± 4, 193 ± 10 and >5000 μM, and for transcriptional inhibition they were 12 ± 1.8, 75 ± 6.5 and >5000 μM for p-, m-NO-ASA and ASA, respectively. p-NO-ASA reduced the expression of Wnt/β-catenin downstream target gene cyclin D1, and total cellular β-catenin levels. COX-2 expression was induced by p-NO-ASA, protein kinase C inhibitors reversed this induction. p-NO-ASA blocked the cell cycle transition at S to G2/M phase. These studies suggest a targeted chemopreventive/chemotherapeutic potential for NO-ASA against breast cancer. © 2009 Elsevier Inc. All rights reserved.

Link to Full Text

Share

COinS