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

Abstract
There is current evidence implicating the Wnt/beta-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 beta-catenin/TCF signaling. The p- and m-NO-ASA isomers strongly inhibited cell growth and beta-catenin/TCF transcriptional activity compared to ASA; the IC50s for growth inhibition were 57+/-4, 193+/-10 and >5000microM, and for transcriptional inhibition they were 12+/-1.8, 75+/-6.5 and >5000microM for p-, m-NO-ASA and ASA, respectively. p-NO-ASA reduced the expression of Wnt/beta-catenin downstream target gene cyclin D1, and total cellular beta-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.
AuthorsNiharika Nath, Rashida Vassell, Mitali Chattopadhyay, Marsel Kogan, Khosrow Kashfi
JournalBiochemical pharmacology (Biochem Pharmacol) Vol. 78 Issue 10 Pg. 1298-304 (Nov 15 2009) ISSN: 1873-2968 [Electronic] England
PMID19576865 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticarcinogenic Agents
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • CTNNB1 protein, human
  • DNA-Binding Proteins
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors
  • Wnt Proteins
  • beta Catenin
  • Cyclin D1
  • Cyclooxygenase 2
  • nitroaspirin
  • Aspirin
Topics
  • Anticarcinogenic Agents (chemistry, pharmacology)
  • Aspirin (analogs & derivatives, chemistry, pharmacology)
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Breast Neoplasms (enzymology, metabolism, pathology, prevention & control)
  • Cell Cycle (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cyclin D1 (genetics)
  • Cyclooxygenase 2 (biosynthesis)
  • DNA-Binding Proteins (biosynthesis, genetics)
  • Down-Regulation
  • Enzyme Induction
  • Female
  • Genes, Reporter
  • Humans
  • Inhibitory Concentration 50
  • Isomerism
  • Signal Transduction (drug effects)
  • Transcription Factor 4
  • Transcription Factors (biosynthesis, genetics)
  • Transcription, Genetic (drug effects)
  • Wnt Proteins (biosynthesis, genetics)
  • beta Catenin (biosynthesis, genetics)

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