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.
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Authors | Niharika Nath, Rashida Vassell, Mitali Chattopadhyay, Marsel Kogan, Khosrow Kashfi |
Journal | Biochemical pharmacology
(Biochem Pharmacol)
Vol. 78
Issue 10
Pg. 1298-304
(Nov 15 2009)
ISSN: 1873-2968 [Electronic] England |
PMID | 19576865
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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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
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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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