Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea.
Nutrients. 2019 Sep 5;11(9):2113. doi: 10.3390/nu11092113.
Reactive oxygen species (ROS) contribute to the oncogenic phenotype of cancer cells by acting as signaling molecules for inducing proliferation. ROS are known to activate the epidermal growth factor receptor (EGFR), which causes the activation of the Ras/mitogen-activated protein kinases (MAPKs) pathway. The Ras-dependent pathway promotes the activation of nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB), a transcriptional modulator of cyclooxygenase-2 (COX-2) that induces cell proliferation. Lycopene is a potent antioxidant carotenoid and is responsible for the red color of fruits and vegetables. This study aims to investigate whether lycopene inhibits proliferation and induces apoptosis in gastric cancer AGS cells by suppressing the EGFR/Ras/MAPK and NF-κB-COX-2 signaling axis. Lycopene decreased cell viability and increased apoptotic indices (DNA fragmentation, apoptosis inducing factor, cleavage of caspase-3 and caspase-9, Bax/Bcl-2 ratio). Lycopene reduced the level of intracellular and mitochondrial ROS and decreased the activation of the ROS-mediated EGFR/Ras/extracellular signal-regulated kinase (ERK) and p38 MAPK pathways, thus leading to attenuation of the DNA-binding activity of NF-κB p50/p50 and the level of COX-2 gene expression. These results show that lycopene-induced apoptosis and inhibition of proliferation occur via inhibition of ROS-activated EGFR/Ras/ERK and p38 MAPK pathways and NF-κB-mediated COX-2 gene expression in AGS cells. In conclusion, consumption of lycopene-enriched foods could decrease the incidence of gastric cancer.
活性氧 (ROS) 通过作为诱导增殖的信号分子，促进癌细胞的致癌表型。ROS 已知可激活表皮生长因子受体 (EGFR)，导致 Ras/丝裂原活化蛋白激酶 (MAPKs) 途径的激活。Ras 依赖性途径促进核因子-κB 轻链增强子的激活 B 细胞 (NF-κB)，NF-κB 是环氧化酶-2 (COX-2) 的转录调节剂，诱导细胞增殖。番茄红素是一种有效的抗氧化类胡萝卜素，负责水果和蔬菜的红色。本研究旨在探讨番茄红素是否通过抑制 EGFR/Ras/MAPK 和 NF-κB-COX-2 信号轴抑制增殖并诱导胃癌 AGS 细胞凋亡。番茄红素降低细胞活力并增加凋亡指数（DNA 片段化、凋亡诱导因子、caspase-3 和 caspase-9 的裂解、Bax/Bcl-2 比值）。番茄红素降低细胞内和线粒体 ROS 的水平，并降低 ROS 介导的 EGFR/Ras/细胞外信号调节激酶 (ERK) 和 p38 MAPK 途径的激活，从而减弱 NF-κB p50/p50 的 DNA 结合活性和 COX-2 基因表达水平。这些结果表明，番茄红素诱导的凋亡和增殖抑制是通过抑制 ROS 激活的 EGFR/Ras/ERK 和 p38 MAPK 途径以及 NF-κB 介导的 COX-2 基因表达在 AGS 细胞中发生的。总之，食用富含番茄红素的食物可能会降低胃癌的发病率。
