Department of Food and Nutrition, College of Human Ecology, Yonsei University, Seoul 03722, Republic of Korea.
Molecules. 2023 Jan 25;28(3):1178. doi: 10.3390/molecules28031178.
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 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.
细胞凋亡的紊乱导致癌细胞的进展；因此，抗癌剂针对癌细胞的细胞凋亡。活性氧（ROS）通过激活半胱天冬酶和半胱天冬酶依赖性核酸酶诱导细胞凋亡，导致 DNA 片段化。ROS 增加促凋亡蛋白 Bax 的表达，这是由核因子-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，其激活参与细胞凋亡。叶黄素，一种含氧类胡萝卜素和已知的抗氧化剂，存在于绿叶深绿色蔬菜如菠菜和羽衣甘蓝中，以及黄色食物如玉米和蛋黄中。大量叶黄素增加 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通过激活 NADPH 氧化酶产生 ROS 并诱导胃癌 AGS 细胞凋亡。叶黄素通过增加 NADPH 氧化酶亚基 p47 向细胞膜的易位来增加 ROS 水平并促进 NADPH 氧化酶的激活。它增加了 NF-κB 的激活和促凋亡指标，如 Bax、caspase-3 切割和 DNA 片段化，并降低了 AGS 细胞中的 Bcl-2、细胞活力和集落形成。特异性 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 AGS 细胞死亡、DNA 片段化和 NF-κB DNA 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，其介导 NF-κB 激活和胃癌 AGS 细胞凋亡。因此，叶黄素的补充可能有益于增加胃癌细胞中 ROS 介导的细胞凋亡。
