Anti-gastric cancer activity and mechanism of natural compound "Heilaohulignan C" isolated from Kadsura coccinea
Anti-gastric cancer activity and mechanism of natural compound "Heilaohulignan C" isolated from Kadsura coccinea
复制标题
DOI：
10.1002/ptr.7114
复制
发表时间：
2021-06-21
影响因子：
7.2
通讯作者：
Yuhui, Qin
中科院分区：
文献类型：
--
作者：
Daniyal, Muhammad;Liu, Yongbei;Yuhui, Qin
在本研究中，我们分析了一种新化合物海拉湖木脂素C(B-6)对人胃癌细胞的抗肿瘤活性。四甲基偶氮唑盐、细胞迁移、钙调素/碘化丙啶(PI)和流式细胞仪检测BGC-823细胞株(胃肿瘤)。用蛋白质印迹法鉴定蛋白质水平。采用裸鼠移植瘤进行体内抗癌分析。毒性研究采用H&E染色和实验室研究。四甲基偶氮唑盐(MTT)法检测BGC-823细胞的细胞毒作用，钙调素/碘化丙啶(PI)检测显示高剂量B-6作用后死亡细胞比例增加，流式细胞仪(FACS)检测表明B-6通过诱导细胞凋亡而影响胃癌细胞。Western印迹分析证实，(B-6)可降低Bc l-2的表达，上调P53、Bax的表达，并裂解Caspase-3，从而证实B-6通过caspase和细胞色素C途径进行细胞凋亡。此外，B-6特别能降低异种移植小鼠的肿瘤体积和肿瘤大小。H&E染色还支持B-6对正常组织没有任何毒性影响。本研究支持B-6通过P53和线粒体依赖的细胞凋亡途径发挥抗胃癌的药理作用，且对正常组织无毒性。
In this research, we analyzed the antitumor activity of one new compound Heilaohulignan C (B-6) on the human gastric carcinoma cells. MTT, cell migration, Calcein AM/Propidium Iodide (PI), and flow cytometry in BGC-823 cell line (gastric tumor). Western blot was utilized to distinguish the protein level. Xenografts nude mice were used for in vivo anticancer analysis. H&E staining and laboratory investigation was accomplished for toxicity study. MTT test demonstrated the cytotoxicity of BGC-823 cells, Calcein AM/Propidium Iodide (PI) examine indicated increment dead cells proportion with a high dose of B-6, Flow cytometry (FACS) measure showed that B-6 influenced gastric cancer cells by initiating apoptosis. Western blot analysis confirmed that (B-6) decrease the level of Bcl-2 and increase the level of p53, Bax, and cleaved Caspase-3, this confirms that the B-6 doing the apoptosis through caspase and cytochrome C apoptotic pathways. Also, B-6 particularly decline the tumor volume and tumor size in the xenograft mice. H&E staining additionally supports that B-6 does not have any toxic impact on the normal tissues. This research supports that B-6 have pharmacological activity against gastric cancer, by p53 and mitochondrial dependent apoptotic pathway, and have no toxicity on normal tissues.