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.
Highlights
Prostate cancer (PCa) is the most common reproductive system cancer in elderly men
We concluded that the effects of arecoline on the growth of normal RWPE-1 and cancerous PC-3 and LNCaP prostate cells are likely mediated through cell cycle dysregulation (Figure 11)
The effects are related to the induction of different phases of growth arrest as well as alterations in the levels of specific members of the cyclin-dependent kinase (CDK), CDK inhibitor (CKI), and cyclin protein families and are induced in a reactive oxygen species (ROS)-dependent manner
Summary
Prostate cancer (PCa) is the most common reproductive system cancer in elderly men. The American Cancer Society estimated that 180,890 new cases of PCa occurred in the US in 2016 and that approximately 26,120 deaths occurred that same year from PCa-specific disease. Various in vivo studies in rats have shown that arecoline may stimulate Leydig cell activity and the release of testosterone possibly via the inhibition of pineal activity [5]. Despite this evidence that arecoline has an indirect impact on the rat prostate gland through the modulation of testosterone levels, it is still unknown whether arecoline exerts direct, differential effects on normal and cancerous human prostate cells. It is worthwhile to explore whether arecoline or other BNAs differentially affect the growth of normal prostate cells, androgen-independent PCa cells, and androgen-dependent PCa cells
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