Abstract | INTRODUCTION: METHODS: RESULTS: Under conditions by which JS-K was not cytotoxic, JS-K significantly decreased (P < 0.05) the invasiveness of breast cancer cells across the Matrigel basement membrane, which was directly correlated with NO production. JS-43-126, a non-NO-releasing analog of JS-K, had no effect on NO levels or invasion. JS-K increased (P < 0.05) TIMP-2 production, and blocking TIMP-2 activity with a neutralizing antibody significantly increased (P < 0.05) the invasive activity of JS-K-treated cells across Matrigel. JS-K decreased p38 activity, whereas the activity and the expression of extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase were unaffected. CONCLUSION: We report the novel findings that JS-K inhibits breast cancer invasion across the Matrigel basement membrane, and NO production is vital for this activity. Upregulation of TIMP-2 production is one mechanism by which JS-K mediates its anti-invasive effects. JS-K and other NO prodrugs may represent an innovative biological approach in the prevention and treatment of metastatic breast cancer.
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Authors | Ann-Marie Simeone, Vanity McMurtry, René Nieves-Alicea, Joseph E Saavedra, Larry K Keefer, Marcella M Johnson, Ana M Tari |
Journal | Breast cancer research : BCR
(Breast Cancer Res)
Vol. 10
Issue 3
Pg. R44
( 2008)
ISSN: 1465-542X [Electronic] England |
PMID | 18474097
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
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Chemical References |
- Antineoplastic Agents
- Azo Compounds
- Drug Combinations
- Laminin
- O(2)-(2,4-dinitrophenyl) 1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate
- Piperazines
- Prodrugs
- Proteoglycans
- matrigel
- Tissue Inhibitor of Metalloproteinase-2
- Nitric Oxide
- Collagen
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Topics |
- Antineoplastic Agents
(pharmacology)
- Azo Compounds
(pharmacology)
- Basement Membrane
(metabolism)
- Breast Neoplasms
(drug therapy, pathology)
- Cell Line, Tumor
- Cell Proliferation
- Collagen
(chemistry)
- Drug Combinations
- Enzyme-Linked Immunosorbent Assay
- Humans
- Laminin
(chemistry)
- Models, Chemical
- Neoplasm Invasiveness
- Neoplasm Metastasis
- Nitric Oxide
(metabolism)
- Piperazines
(pharmacology)
- Prodrugs
(pharmacology)
- Proteoglycans
(chemistry)
- Tissue Inhibitor of Metalloproteinase-2
(metabolism)
|