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Suppression of Hormone-refractory Prostate Cancer by a Novel Nuclear Factor B Inhibitor in Nude Mice

Department of Urology, Keio University, School of Medicine, Tokyo 160-8582 [E. K., Y. H., J. N., K. K., M. O., T. O., M. M.], and Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama 223-0061 [N. T., Y. S., K. U.] Japan

We have synthesized and explored the feasibility of using a novel nuclear factor (NF) B inhibitor, a dehydroxymethylepoxyquinomicin designated as DHMEQ, against prostate cancer. The activity of NFB, evaluated by transient transfection of a luciferase reporter DNA containing a specific binding sequence for NFB, was inhibited by DHMEQ in three human hormone-refractory prostate cancer cell lines, DU145, JCA-1, and PC-3. Statistically significant growth inhibition was achieved by 20 µg/ml of DHMEQ, and marked levels of apoptosis were induced 48 h after DHMEQ administration in vitro. Electrophoretic mobility shift assay showed that DHMEQ completely inhibited NFB DNA binding activity in JCA-1 cells. Furthermore, i.p. administrations of DHMEQ significantly inhibited pre-established JCA-1 s.c. tumor growth in nude mice without any side effects. Our result indicates the possibility of using a novel NFB activation inhibitor, DHMEQ, as a new treatment strategy against hormone-refractory prostate cancer.

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