Nobiletin, a citrus polymethoxyflavone, enhances the effects of bicalutamide on prostate cancer cells<i>via</i>down regulation of NF-κB, STAT3, and ERK activation
Yuran Ma, Xiangshan Ren, Nandini Patel, Xue-Tao Xu, Panpan Wu, Wenfeng Liu, Kun Zhang, Susan Goodin, Dongli Li, Xi Zheng
Abstract
Natural products have shown potential to be combined with current cancer therapies to improve patient outcomes. Nobiletin (NBT) is a citrus polymethoxyflavone and has been shown to exert an anticancer effect in various cancer cells. We investigated the effects and mechanisms of NBT in combination with bicalutamide (BCT), a commonly used anti-androgen drug in prostate cancer therapy, on prostate cancer cells. Our results demonstrate that the combined treatment with NBT and BCT produces an enhanced inhibitory effect on the growth of prostate cancer cells compared to either compound alone. The synergistic action of NBT and BCT was confirmed using isobologram analysis. Moreover, this study has shown that NBT and BCT synergistically inhibited colony formation and migration as well as induced apoptosis. Mechanistic studies demonstrate that NBT and BCT combination reduced key cellular signaling regulators including: p-Erk/Erk, p-STAT3/STAT3 and NF-κB. Overall, these results suggest that NBT combination with BCT may be an effective treatment for prostate cancer.