TY - JOUR
T1 - Betel nut arecoline induces different phases of growth arrest between normal and cancerous prostate cells through the reactive oxygen species pathway
AU - Shih, Li Jane
AU - Wang, Jia Yu
AU - Jheng, Jing Yao
AU - Siao, An Ci
AU - Lin, Yen Yue
AU - Tsuei, Yi Wei
AU - Kuo, Yow Chii
AU - Chuu, Chih Pin
AU - Kao, Yung Hsi
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
KW - Areca nut
KW - Cell cycle
KW - Cyclin
KW - Cyclin‐dependent kinase
KW - P21
KW - Prostate cancer
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85097093968&partnerID=8YFLogxK
U2 - 10.3390/ijms21239219
DO - 10.3390/ijms21239219
M3 - 期刊論文
C2 - 33287214
AN - SCOPUS:85097093968
SN - 1661-6596
VL - 21
SP - 1
EP - 18
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 23
M1 - 9219
ER -