Herein we, for the first time, investigated a potential synergistic effect of nobiletin (NOB) and sorafenib (SOR) on PC-3 prostate cancer and HUVEC control cell lines. In order to determine the cytotoxic and apoptotic effects of the combination of NOB and SOR, WST-1, Annexin V, and cell cycle analysis were performed. The potential molecular mechanism of apoptotic cell death was assessed by , , , , and gene expression and acridine orange (AO) and DAPI staining. Our results indicated that NOB and SOR combination had a significant inhibitory effect on the viability of PC-3 cells with less toxicity on HUVEC cells than SOR alone ( < 0.01). NOB and SOR combination significantly caused much more apoptotic cell death and cell cycle arrest at G0/G1 phase by up-regulation of , , and levels in PC-3 cells ( < 0.01). Therefore, strong synergistic effects between NOB and SOR were analyzed (CI < 1). NOB and SOR combination was more effective than SOR and NOB alone and reduced the exposure time for SOR and NOB in PC-3 cells. Combination strategy is a therapeutic potential to improve efficacy and reduce side-effect of SOR for the treatment of metastatic prostate cancer cells.
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