Department of Gastroenterology, People's Hospital of Zhangqiu, 250200, Jinan, Shandong Province, China.
Department of General Surgery, People's Hospital of Zhangqiu, 250200, Jinan, Shandong Province, China.
Dokl Biochem Biophys. 2021 Sep;500(1):393-401. doi: 10.1134/S1607672921050070. Epub 2021 Oct 25.
Andrographolide is a labdane diterpenoid isolated from Andrographis paniculata. The plant extract and andrographolide has long been used in traditional medicine practices mainly for gastrointestinal diseases and improving liver function. Andrographolide has shown various pharmacological properties including anti-inflammatory, antioxidant and anticancer activity. This study evaluated the effect of andrographolide on proliferation of human gastric carcinoma cells in relevance to p53 and Mdm-2 pathways. Andrographolide inhibited the proliferation of SGC7901 and AGS cells in a dose-dependent manner with estimated IC values 38 and 44 μM respectively. Effect of andrographolide on p53 activity was ascertained by using a p53 activator (RITA) which showed synergistic inhibition of cell proliferation. While andrographolide when used in combination with a p53 inhibitor (pifithrin-α) showed potent restriction over its response. Andrographolide caused decrease in mitochondrial membrane potential as an indicator of apoptotic activity. Andrographolide activated the expression of p53 protein and gene and downregulated the levels of Mdm-2 (negative regulator of p53). Andrographolide inhibited the colony formation abilities in SGC7901 in a p53-dependent manner followed by induction of mitochondrial intrinsic apoptosis through activation of caspases-9 and -3, cleavage of PARP, and inhibition of pro-apoptotic Bcl-2. Andrographolide induced p53 mediated apoptosis in gastric carcinoma cells which adds to a novel approach in anticancer therapies.
穿心莲内酯是一种从穿心莲中分离得到的裂环烯醚萜二萜。该植物提取物和穿心莲内酯在传统医学实践中一直被用于治疗胃肠道疾病和改善肝功能。穿心莲内酯具有多种药理作用，包括抗炎、抗氧化和抗癌活性。本研究评估了穿心莲内酯对人胃癌细胞增殖的影响及其与 p53 和 Mdm-2 通路的关系。穿心莲内酯以剂量依赖的方式抑制 SGC7901 和 AGS 细胞的增殖，其估计 IC 值分别为 38 和 44 μM。通过使用 p53 激活剂（RITA）来确定穿心莲内酯对 p53 活性的影响，结果显示其对细胞增殖具有协同抑制作用。而穿心莲内酯与 p53 抑制剂（pifithrin-α）联合使用时，对其反应具有更强的限制作用。穿心莲内酯导致线粒体膜电位下降，作为细胞凋亡活性的指标。穿心莲内酯激活了 p53 蛋白和基因的表达，下调了 Mdm-2（p53 的负调节剂）的水平。穿心莲内酯以 p53 依赖的方式抑制 SGC7901 的集落形成能力，随后通过激活 caspase-9 和 -3、裂解 PARP 和抑制促凋亡 Bcl-2，诱导线粒体内在凋亡。穿心莲内酯诱导胃癌细胞中的 p53 介导的细胞凋亡，为癌症治疗提供了一种新方法。
