Apigetrin is a flavonoid glycoside phytonutrient derived from fruits and vegetables that is well known for a variety of biological activities such as antioxidant and anti-inflammatory activities. In the current study, we determined the effect of apigetrin on AGS gastric cancer cell. Apigetrin reduced cancer cell proliferation and induced G2/M phase cell cycle arrest by regulating cyclin B1, cdc25c and cdk1 protein expression in AGS cell. Apigetrin treatment caused apoptotic cell death in AGS cells, characterized by the accumulation of apoptosis portion, cleavage of caspase-3 and poly ADP-ribose polymerase (PARP). Apigetrin-treated cells increased the expression of extrinsic apoptosis pathway proteins and mRNA. However, intrinsic apoptosis pathway related proteins were not altered. In addition, AGS cells treated with apigetrin increased autophagic cell death, featured by the formation of autophagic vacuole and acidic vesicular organelles. Autophagy marker proteins, such as LC3B-II and beclin-1, were increased, and p62, an autophagy flux marker protein, was also increased by endoplasmic reticulum stress. Also, the phosphorylation of PI3K/AKT/mTOR pathway proteins and its downstream targets in apigetrin-treated AGS cells was identified to be decreased. Taken together, these data suggest that apigetrin-treated AGS cells induced G2/M phase cell cycle arrest, extrinsic apoptosis and autophagic cell death through PI3K/AKT/mTOR pathway, which can lead to the inhibition of gastric cancer development. Thus, our findings strongly indicate that apigetrin is a basic natural derived compound that could be used as a nutrient source with potential anticancer activities against gastric cancer.

芹菜素是从水果和蔬菜中提取的类黄酮糖苷植物营养素，以多种生物活性（例如抗氧化剂和抗炎活性）而闻名。在当前的研究中，我们确定了芹菜素对AGS胃癌细胞的作用。芹菜素通过调节AGS细胞中的细胞周期蛋白B1，cdc25c和cdk1蛋白表达来减少癌细胞增殖并诱导G2 / M期细胞周期停滞。芹菜素处理引起AGS细胞凋亡，其特征在于凋亡部分的积累，caspase-3的切割和聚ADP-核糖聚合酶（PARP）的裂解。芹菜素处理的细胞增加了外在凋亡途径蛋白和mRNA的表达。但是，内在的凋亡途径相关蛋白没有改变。此外，用apigetrin处理的AGS细胞增加自噬细胞死亡，其特征在于自噬泡和酸性水泡细胞器的形成。自噬标记蛋白，例如LC3B-II和beclin-1，增加了，内质网应激也增加了自噬通量标记蛋白p62。同样，在apigetrin处理的AGS细胞中，PI3K / AKT / mTOR途径蛋白及其下游靶点的磷酸化被确定为降低。综上所述，这些数据表明用apigetrin处理的AGS细胞通过PI3K / AKT / mTOR途径诱导了G2 / M期细胞周期停滞，外源性凋亡和自噬细胞死亡，这可能导致胃癌的发展受到抑制。从而，