Nobiletin, a citrus polymethoxyflavone, enhances the effects of bicalutamide on prostate cancer cells via down regulation of NF-κB, STAT3, and ERK activation

  • RSC Adv. 2020 Mar 10;10(17):10254-10262. doi: 10.1039/c9ra10020b.
Yuran Ma  1 ,  Xiang Ren  1 ,  Nandini Patel  2 ,  Xuetao Xu  1  3 ,  Panpan Wu  1 ,  Wenfeng Liu  1  3 ,  Kun Zhang  1  3 ,  Susan Goodin  4 ,  Dongli Li  1  3 ,  Xi Zheng  2  4
Affiliations
  • 1. School of Biotechnology and Health Sciences, Wuyi University Jiangmen Guangdong 529020 China.
  • 2. Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey 164 Frelinghuysen Road Piscataway NJ 08854 USA [email protected] +1-732-445-0687 +1-848-445-8069.
  • 3. International Healthcare Innovation Institute (Jiangmen) Jiangmen 529020 Guangdong China.
  • 4. Rutgers Cancer Institute of New Jersey New Brunswick NJ 08903 USA.
PMID: 35498570 DOI: 10.1039/c9ra10020b
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.

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