(P001) DMAPT Inhibits NF-KAPPA B Activity and Increases Sensitivity of Prostate Cancer Cells to X-Rays In Vitro and in Tumor Xenografts In Vivo

Constitutive activation of the pro-survival transcription factor NF-κB has been associated with resistance to both chemotherapy and radiation therapy in many human cancers, including prostate cancer. Our lab and others have demonstrated that the natural product parthenolide is able to inhibit NF-κB activity and sensitize PC-3 prostate cancers cells to X-rays in vitro; however, parthenolide has poor bioavailability in vivo and therefore has little clinical utility in this regard. We show here that treatment of PC-3 and DU145 human prostate cancer cells with Dimethyl-amino-parthenolide (DMAPT), a parthenolide derivative with increased bioavailability, inhibits constitutive and radiation-induced NF-kB binding activity and slows prostate cancer cell growth.

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