Document Type
Article
Publication Date
6-15-2009
Publication Title
Biochemical Pharmacology
Abstract
Epidemiological and animal model studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs) can act as chemopreventive agents. The cyclooxygenase-2 (COX-2) inhibitor nimesulide shows anti-cancer effect in different type of cancers. In the current study, five breast carcinoma cell lines were used to explore the anti-cancer mechanisms of a nimesulide derivative compound 76. The compound dose dependently suppressed SKBR-3, BT474 and MDA-MB-453 breast cancer cell proliferation with IC50 of 0.9 μM, 2.2 μM and 4.0 μM, respectively. However, it needs much higher concentrations to inhibit MCF-7 and MDA-MB-231 breast cancer cell growth with IC50 at 22.1 μM and 19.6 μM, respectively. Further investigation reveals that compound 76 induced apoptosis in SKBR-3 and BT474 cells. Since these cells are Her2 overexpressing cells, the Her2 intracellular signaling pathways were examined after the treatment. There was no significant changing of kinase activity. However, the cytochrome c release assay indicated that the apoptosis induced by the compound was mediated by the mitochondria. These results suggest that compound 76 selectively induce apoptosis in Her2 overexpressing breast cancer cells through the mitochondria, and could be used as a lead to design more potent derivatives.
Recommended Citation
Chen, Bin; Su, Bin; and Chen, Shiuan, "A COX-2 Inhibitor Nimesulide Analog Selectively Induces Apoptosis in Her2 Overexpressing Breast Cancer Cells via Cytochrome C Dependent Mechanisms" (2009). Chemistry Faculty Publications. 373.
https://engagedscholarship.csuohio.edu/scichem_facpub/373
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
DOI
10.1016/j.bcp.2009.03.015
Version
Postprint
Volume
77
Issue
12
Comments
This work was supported by grants from the National Institutes of Health CA44735 (SC), ES08528 (SC).