| Summary: | 碩士 === 國立中央大學 === 生命科學系 === 105 === Betel nut alkaloids (BNAs), especially arecoline, possesses multiple biological activities. Although arecoline was found from our laboratory to induce the G2/M growth arrest of normal human RWPE-1 prostate cells and the respective G2/M and G0/G1 growth arrests of human PC-3 and LNCaP prostate cancer cells, the exact mechanisms of its differential actions are still not clear. Using all the three cell lines, we investigated cell cycle controlling proteins involved in differential arecoline modulations of normal and cancerous prostate cell growth arrests. In RWPE-1 cells, arecoline induced increases in CDK1, p21, and cyclins B1 and D3 proteins and no significant effects in CDK2, CDK4, and cyclin D1 protein levels. In PC-3 cells, arecoline tended to decrease levels of CDK1, p21, p27, cyclin D1, and cyclin D3 proteins and increase cyclin B1 levels, but it had no effects on CDK4 and CDK6 proteins. In LNCaP cells, arecoline induced decreases in CDK2, CDK4, and cyclin D1 proteins, increases in p21, p27, and cyclin D3 proteins, and no effects on CDK1 and cyclin B1 proteins. These data suggest that arecoline regulates the cell cycles of normal and cancerous prostate cells in CDK subfamily-, cyclin subfamily-, and CKI subfamily-dependent manners. Interestingly, pretreatment with the antioxidant N-acetylcysteine (NAC) blocked the arecoline induced increases in CDK1 and cyclins B1 and D3 but not p21 proteins in RWPE-1 cells, while NAC prevented arecoline-induced decreases in CDK2 but not CDK1 proteins and arecoline-increased cyclin B1 protein levels in PC-3 cell. In LNCaP cells, NAC blocked arecoline-decreased levels of CDK2, CDK4 and cyclin D1 proteins and suppressed arecoline-increased levels of p21, p27, and cyclin D3 proteins. These data suggest that the oxidant activity of arecoline made different impacts on cell cycle controlling proteins between normal and cancerous prostate cancer cells and thereby inducing different phases of their growth arrests.
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