| Summary: | 碩士 === 國立中央大學 === 生命科學系 === 102 === Betel nut, a common substance consumed in Asia, including Taiwan, contains four major alkaloids, such as arecoline, arecaidine, guvacoline, and guvacine. Although betel nut alkaloids (BNAs), particularly arecoline, were found to increase blood testosterone level and prostate gland growth in rats, a clear relationship between BNAs and human prostate cancer cells was not reported. Using normal(i.e., RWPE-1) and cancerous human prostate(i.e., LNCaP-FGC、-104-S、-104-R1、-104-R2, and PC-3) cells, we observed that arecoline, but not arecaidine or guvacine, significantly reduced cell viability of these prostate cells, in dose-dependent and time-dependent manners. Flow cytometric analysis indicated that arecoline arrest normal RWPE-1 cells and PC-3 cancer cells at G2/M phase of their cell cycle, and it reduced G1 phase of their cell cycle. However, arecoline induced increase of the G1 and Sub-G1 phase and decrease of the S phase in the cell cycle of LNCaP-FGC、-104-R1, and -104-R2 prostate cancer cells. And, arecoline induced increase of the Sub-G1 phase in the cell cycle of LNCaP-104-S prostate cancer cells. In addition, arecoline but not guvacine induced the production of radical oxygen species (ROS) from normal and cancerous human prostate cells. Interestingly, we found that arecoline and guvacine, but not arecaidine, significantly reduced cell migration of prostate cancer cells in dose-dependent manners. RWPE1 cells did not migrate. Although arecoline was reported as a muscarinic acetylcholine receptor (mAChR) agonist from other cell studies, pretreatment with a mAChR antagonist atropine did not alter the arecoline-induced cell viability, ROS production, or migration of PC-3 and LNCaP cancer cells. Atropine neither altered the arecoline induced cell viability and ROS production of RWPE1 prostate cell nor changed the guvacine-induced cell migration of LNCaP and PC-3 cancer cells. However, N-acetyl-cysteine (NAC), a glutathione activator, blocked the arecoline-induced changes in the cell viability, ROS production, and diffirent phase of the cell cycle of normal and cancerous human prostate cells. NAC also prevent the arecoline-inhibited but not guvacine-inhibited migration of human prostate cencer cells. These data suggest that arecoline inhibits cell viability and migration of prostate cancer cells through the glutathione-, and ROS-dependent and mAChR-independent pathways. The results also suggest the glutathione-, ROS-, and mAChR-independent effect of guvacine on the migration of prostate cancer cells. We conclude that BNAs mediate growth and cell migration of human prostate cancer cells through the distinct signaling molecule, structure type-dependent, and cell type-dependent pathway.
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