Abstract
e16065 Background: The transcription factor STAT3 is constitutively active in castration-resistant prostate cancer (CRPC) and constitutes a promising therapeutic target. The reactive fungal metabolite galiellalactone (GL), a STAT3-signaling inhibitor, inhibits the growth, both in vitro and in vivo, of prostate cancer cells expressing activated STAT3 and inhibits growth and induces apoptosis of prostate cancer stem cell-like cells expressing pSTAT3. We aim in this study to identify the STAT3 signaling inhibiting mechanism of GL. Methods: A biotinylated analogue of galiellalactone (GL-biot) was synthesized to be used for identification of GL target proteins. The STAT3 inhibitory activity of GL-biot was confirmed with STAT3 luciferase reporter gene assay. The pSTAT3 expressing human prostate cancer cell line DU145 was incubated with GL-biot, followed by streptavidin beads to isolate proteins bound to GL-biot. Localization of GL-biot in DU145 cells was assessed using confocal microscopy. EMSA was performed on...
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