Wang, Chia-ChiChia-ChiWangLiu, Tsung-YunTsung-YunLiuCheng, Chiung-HsiangChiung-HsiangChengTONG-RONG JANCHIA-CHI WANG2020-01-032020-01-0320091879-3177https://scholars.lib.ntu.edu.tw/handle/123456789/444436Areca quid chewing is a major risk factor for oral submucous fibrosis and oral cancer. Clinical evidence suggests that the pathophysiology of the oral diseases is closely associated with immune deterioration. The objective of the present studies was to investigate the pro-apoptotic effect of areca nut extract (ANE) in lymphocytes. Exposure of na?ve splenic lymphocytes to ANE significantly enhanced apoptosis in a time- and concentration-dependent manner. Results from Hoechst staining confirmed the morphological features characteristic of apoptosis in ANE-treated cells. ANE treatment induced the depolarization of mitochondrial membrane potential (Δψm), which preceded the occurrence of apoptosis. In parallel with the disruption of Δψm, ANE induced the release of cytochrome c, and the activation of caspase-9, indicating the activation of the mitochondrion-dependent pathway. Moreover, an increased level in the intracellular reactive oxygen species was detected in ANE-treated lymphocytes undergoing apoptosis. ANE-mediated apoptosis, caspase-9 activation and ROS production, but not Δψm depolarization, were partially but significantly attenuated in the presence of the antioxidant N-acetyl-l-cysteine (NAC). Collectively, these results demonstrated the pro-apoptotic effect of ANE in primary lymphocytes, which was mediated, at least in part, by the activation of the mitochondrion-dependent pathway and oxidative stress. ? 2009 Elsevier Ltd. All rights reserved.[SDGs]SDG3acetylcysteine; caspase 9; cytochrome c; reactive oxygen metabolite; animal cell; animal tissue; apoptosis; article; betel nut; cell structure; controlled study; enzyme activation; enzyme release; immunopathology; male; membrane depolarization; mitochondrial membrane potential; mitochondrion; mouse; mouth cancer; mouth disease; nonhuman; oxidative stress; pathophysiology; risk factor; spleen cell; spleen lymphocyte; staining; Animals; Apoptosis; Areca; Dose-Response Relationship, Drug; Lymphocytes; Male; Membrane Potential, Mitochondrial; Mice; Mice, Inbred BALB C; Nuts; Oxidative Stress; Plant Extracts; Spleen; Time Factors; Areca; Areca catechu; Murinaejournal article10.1016/j.tiv.2009.04.012