Y. Yokoyama, A. Shinohara, Y. Takahashi
Sep 1, 2000
Citations
4
Influential Citations
12
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Quality indicators
Journal
Anticancer research
Abstract
BACKGROUND 7-Hydroxystaurosporine (UCN-01) is a novel antitumor agent as well as a potent inhibitor of a variety of protein kinases with a preference to protein kinase C. Because an intimate interaction exists between PKC signaling and the ER signaling pathways, sex steroid agonists/antagonists might modulate the cytotoxicity of UCN-01. MATERIALS AND METHODS Effects of sex steroid agonists and antagonists on the UCN-01 cytotoxicity were analyzed by MTT assay in MCF-7/WT and MCF-7/ADR, a multiple drug resistance phenotype lacking ER and PR. RESULTS MCF-7/ADR is 23-fold more resistant to UCN-01 than MCF-7. In MCF-7/WT, danazol and mifepristone enhanced the cytotoxicity of UCN-01, while these agents did not exert any significant effects on it in MCF-7/ADR. CONCLUSION These results suggest that danazol or mifepristone might enhance the antitumor activity of UCN-01 in hormone-dependent cancer cells by interacting with PR.