Betel nut arecoline induces different phases of growth arrest between normal and cancerous prostate cells through the reactive oxygen species pathway

Li Jane Shih, Jia Yu Wang, Jing Yao Jheng, An Ci Siao, Yen Yue Lin, Yi Wei Tsuei, Yow Chii Kuo, Chih Pin Chuu, Yung Hsi Kao

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Prostate cancer (PCa) is a reproductive system cancer in elderly men. We investigated the effects of betel nut arecoline on the growth of normal and cancerous prostate cells. Normal RWPE‐ 1 prostate epithelial cells, androgen‐independent PC‐3 PCa cells, and androgen‐dependent LNCaP PCa cells were used. Arecoline inhibited their growth in dose‐ and time‐dependent manners. Arecoline caused RWPE‐1 and PC‐3 cell cycle arrest in the G2/M phase and LNCaP cell arrest in the G0/G1 phase. In RWPE‐1 cells, arecoline increased the expression of cyclin‐dependent kinase (CDK)‐1, p21, and cyclins B1 and D3, decreased the expression of CDK2, and had no effects on CDK4 and cyclin D1 expression. In PC‐3 cells, arecoline decreased CDK1, CDK2, CDK4, p21, p27, and cyclin D1 and D3 protein expression and increased cyclin B1 protein expression. In LNCaP cells, arecoline decreased CDK2, CDK4, and cyclin D1 expression; increased p21, p27, and cyclin D3 expression; had no effects on CDK1 and cyclin B1 expression. The antioxidant N‐acetylcysteine blocked the arecoline‐induced increase in reactive oxygen species production, decreased cell viability, altered the cell cycle, and changed the cell cycle regulatory protein levels. Thus, arecoline oxidant exerts differential effects on the cell cycle through modulations of regulatory proteins.

Original languageEnglish
Article number9219
Pages (from-to)1-18
Number of pages18
JournalInternational Journal of Molecular Sciences
Volume21
Issue number23
DOIs
StatePublished - 1 Dec 2020

Keywords

  • Areca nut
  • Cell cycle
  • Cyclin
  • Cyclin‐dependent kinase
  • P21
  • Prostate cancer
  • Reactive oxygen species

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