凋亡的破坏导致癌细胞的进展;因此,抗癌药物靶向癌细胞的凋亡。活性氧(ROS)通过激活caspase和caspase依赖性DNA酶诱导细胞凋亡,导致DNA断裂.ROS增加凋亡蛋白Bax的表达,它是由核因子-κB(NF-κB)的激活介导的。烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶是内源性ROS的重要来源,它的激活与细胞凋亡有关。叶黄素,一种含氧类胡萝卜素和已知的抗氧化剂,富含绿叶深绿色蔬菜,比如菠菜和羽衣甘蓝,在黄色食物中,如玉米和蛋黄。大量的叶黄素增加ROS水平并表现出抗癌活性。然而,其抗癌机制尚不清楚。本研究旨在确定叶黄素是否激活NADPH氧化酶以产生ROS并诱导胃癌AGS细胞凋亡。叶黄素通过增加NADPH氧化酶亚基p47phox向细胞膜的易位来增加ROS水平并促进NADPH氧化酶的活化。它增加了NF-κB激活和凋亡指数,比如Bax,caspase-3裂解,和DNA片段化,和降低Bcl-2,细胞活力,和AGS细胞中的集落形成。特定的NADPH氧化酶抑制剂ML171和已知的抗氧化剂N-乙酰半胱氨酸逆转了叶黄素诱导的细胞死亡,DNA片段化,和AGS细胞中NF-κBDNA结合活性。这些结果表明,叶黄素诱导的ROS产生依赖于NADPH氧化酶,在胃癌AGS细胞中介导NF-κB活化和凋亡。因此,叶黄素补充可能有利于增加ROS介导的胃癌细胞凋亡。
Disruption of apoptosis leads to cancer cell progression; thus, anticancer agents target apoptosis of cancer cells. Reactive oxygen species (ROS) induce apoptosis by activating caspases and caspase-dependent DNase, leading to DNA fragmentation. ROS increase the expression of apoptotic protein Bax, which is mediated by activation of nuclear factor-κB (NF--κB). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of endogenous ROS, and its activation is involved in apoptosis. Lutein, an oxygenated carotenoid and known antioxidant, is abundant in leafy dark green vegetables, such as spinach and kale, and in yellow-colored foods, such as corn and egg yolk. High amounts of lutein increase ROS levels and exhibit anticancer activity. However, its anticancer mechanism remains unclear. This study aimed to determine whether lutein activates NADPH oxidase to produce ROS and induce apoptosis in gastric cancer AGS cells. Lutein increased ROS levels and promoted the activation of NADPH oxidase by increasing the translocation of NADPH oxidase subunit p47 phox to the cell membrane. It increased NF-κB activation and apoptotic indices, such as Bax, caspase-3 cleavage, and DNA fragmentation, and decreased Bcl-2, cell viability, and colony formation in AGS cells. The specific NADPH oxidase inhibitor ML171, and the known antioxidant N-acetyl cysteine reversed lutein-induced cell death, DNA fragmentation, and NF-κB DNA-binding activity in AGS cells. These results suggest that lutein-induced ROS production is dependent on NADPH oxidase, which mediates NF-κB activation and apoptosis in gastric cancer AGS cells. Therefore, lutein supplementation may be beneficial for increasing ROS-mediated apoptosis in gastric cancer cells.