Enhancement of radiotherapy in prostate cancer by the novel dibenzo(c)chromen-6-one derivate Palomid 529

4820 Radiotherapy (RT) is a common treatment for localized prostate cancer, but can cause important side effects. The therapeutic effect of RT can be enhanced by pharmacological compounds that target specific pathways involved in cell survival. This would elicit a similar therapeutic response using lower doses of RT and, in turn, reducing side effects. We have used the novel dibenzo(c)chromen-6-one (DBC) derivate P529 in combination with RT in PC-3 cells, in vitro and in vivo (in xenograft models). P529 alone produced cytotoxicity in PC-3 cells (IC50= 3 microM). Treatment of PC-3 cells with P529 and RT caused a dramatic decrease in phospho-AKT, VEGF and Id-1. The ratio Bcl2/Bax was also reduced. Doses of 2, 4, and 8 Gy produced 22.3%, 33.4%, 62.3% cell growth inhibition, respectively. Combination of 2μM P529 with 2 Gy RT produced 78.9% growth inhibition. In vivo studies in nude mice xenotransplanted with PC-3 cells and treated with 50 mg/Kg P529 (3 times a week) for 3 weeks, 6 Gy radiotherapy, or combination, resulted in the following tumor volume decrease (as compared to controls): 42.5%, 52.3%, and 76.3% (p=0.005), respectively. Tumors receiving combination therapy showed massive necrotic, apoptotic and fibrotic areas. Proliferation rates in tumours were significantly reduced, as a result of the treatment. Our results demonstrate that the dibenzo(c)chromen-6-one derivate P529 significantly enhances the effect of radiotherapy in prostate cancer.