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3-苯乙酸-5,15-二乙酸瑞香毒素的结构鉴定及体外抗癌活性

Structure Identification and In Vitro Anticancer Activity of Lathyrol-3-phenylacetate-5,15-diacetate.

作者信息

Zhang Jian-Ye, Huang Wen-Jing, Sun Hong-Mei, Liu Yun, Zhao Xiao-Qin, Tang Si-Li, Sun Ming-Na, Wang Sheng, Li Jia-Jun, Zhang Ling-Ling, Zhou Jun-Hua, Pan Qian-Rong, Chen Hu-Biao

机构信息

Key Laboratory of Molecular and Clinical Pharmacology, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.

Infinitus (China) Company Ltd., Jiangmen 529156, China.

出版信息

Molecules. 2017 Aug 25;22(9):1412. doi: 10.3390/molecules22091412.

Abstract

Natural products from the genus show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining and fluorescence microscopy examination were applied to investigate the anticancer activity of the obtained compounds. In a result, lathyrol-3-phenyl- acetate-5,15-diacetate (deoxy Euphorbia factor L1, DEFL1) was isolated from Caper Euphorbia Seed. Moreover, the NMR signals were totally assigned. DEFL1 showed potent inhibition against lung cancer A549 cells, with an IC value of 17.51 ± 0.85 μM. Furthermore, DEFL1 suppressed wound healing of A549 cells in a concentration-dependent manner. Mechanically, DEFL1 induced apoptosis, with involvement of an increase of reactive oxygen species (ROS), decrease of mitochondrial membrane potential (ΔΨm), release of cytochrome , activity raise of caspase-9 and 3. Characteristic features of apoptosis were observed by fluorescence microscopy. In summary, DEFL1 inhibited growth and induced apoptosis in lung cancer A549 cells via a mitochondrial pathway.

摘要

大戟属的天然产物具有吸引注意力的活性,如抗癌活性。在本文中,采用经典的分离和结构鉴定方法对续随子种子进行了研究。随后,运用MTT和伤口愈合试验、流式细胞术、蛋白质免疫印迹法、Hoechst 33258染色和荧光显微镜检查来研究所得化合物的抗癌活性。结果从续随子种子中分离出了瑞香烷型二萜酯类化合物lathyrol-3-phenyl- acetate-5,15-diacetate(去氧大戟因子L1,DEFL1)。此外,对其核磁共振信号进行了全归属。DEFL1对肺癌A549细胞显示出强效抑制作用,IC值为17.51±0.85μM。此外,DEFL1以浓度依赖的方式抑制A549细胞的伤口愈合。机制上,DEFL1诱导细胞凋亡,涉及活性氧(ROS)增加、线粒体膜电位(ΔΨm)降低、细胞色素c释放、半胱天冬酶-9和3活性升高。通过荧光显微镜观察到了凋亡的特征。综上所述,DEFL1通过线粒体途径抑制肺癌A549细胞的生长并诱导其凋亡

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c14e/6151716/10348bf9f795/molecules-22-01412-g001.jpg

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