Abstract
Carboxyamidotriazole (CAI) is a calcium influx inhibitor that is undergoing clinical trials for the treatment of various human cancers following the identification of its antiproliferative and antimetastatic activities. The exact mechanism of its action is not clearly understood, and whether it has other functions besides the established antitumor activity has not been reported either. In the present study, we demonstrate for the first time that CAI possesses anti-inflammatory and analgesic activities using a variety of animal models, including croton oil-induced ear edema, cotton-induced granuloma, rat adjuvant-induced arthritis, acetic acid-induced writhing, and the formalin test. We also show that CAI significantly inhibits local vascular permeability stimulated by vascular endothelial growth factor or histamine and decreases tumor necrosis factor-α and interleukin-1β levels at the site of inflammation and in serums, which may contribute to the anti-inflammatory effect. These data suggest that CAI is a promising anti-inflammatory and analgesic agent, and they provide new insight into the biological activity of the drug.
Footnotes
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This work was supported by the National High Technology Research and Development Program of China (2005AA2Z3G41) and a grant of international cooperation from the Ministry of Science and Technique of China (2005DFA31110).
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L.G. and C.Y. contributed equally to this work.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.107.131888.
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ABBREVIATIONS: CAI, carboxyamidotriazole; TNF, tumor necrosis factor; IL, interleukin; PEG, polyethylene glycol; ELISA, enzyme-linked immunosorbent assay; NS, 0.9% NaCl; VEGF, vascular endothelial growth factor; PLC, phospholipase C.
- Received September 19, 2007.
- Accepted January 7, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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