Suppression of hormone-refractory prostate cancer by a novel nuclear factor κB inhibitor in nude mice

We have synthesized and explored the feasibility of using a novel nuclear factor (NF) κB inhibitor, a dehydroxymethylepoxyquinomicin designated as DHMEQ, against prostate cancer. The activity of NFκB, evaluated by transient transfection of a luciferase reporter DNA containing a specific binding sequence for NFκB, 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 NFκB 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 NFκB activation inhibitor, DHMEQ, as a new treatment strategy against hormone-refractory prostate cancer.