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从中国本土藤黄属植物中鉴定和表征靶向细胞凋亡和自噬的抗癌化合物。

Identification and characterization of anticancer compounds targeting apoptosis and autophagy from Chinese native Garcinia species.

作者信息

Xu Danqing, Lao Yuanzhi, Xu Naihan, Hu Hui, Fu Wenwei, Tan Hongsheng, Gu Yunzhi, Song Zhijun, Cao Peng, Xu Hongxi

机构信息

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, P. R. China.

出版信息

Planta Med. 2015 Jan;81(1):79-89. doi: 10.1055/s-0034-1383356. Epub 2014 Dec 5.

Abstract

Natural compounds from medicinal plants are important resources for drug development. Active compounds targeting apoptosis and autophagy are candidates for anti-cancer drugs. In this study, we collected Garcinia species from China and extracted them into water or ethanol fractions. Then, we performed a functional screen in search of novel apoptosis and autophagy regulators. We first characterized the anti-proliferation activity of the crude extracts on multiple cell lines. HeLa cells expressing GFP-LC3 were used to examine the effects of the crude extracts on autophagy. Their activities were confirmed by Western blots of A549 and HeLa cells. By using bioassay guided fractionation, we found that two caged prenylxanthones from Garcinia bracteata, neobractatin and isobractatin, can significantly induce apoptosis and inhibit autophagy. Our results suggest that different Garcinia species displayed various degrees of toxicity on different cancer cell lines. Furthermore, the use of a high content screening assay to screen natural products was an essential method to identify novel autophagy regulators.

摘要

药用植物中的天然化合物是药物开发的重要资源。靶向细胞凋亡和自噬的活性化合物是抗癌药物的候选物。在本研究中,我们收集了来自中国的藤黄属植物,并将其提取成水相或乙醇相馏分。然后,我们进行了功能筛选以寻找新型的细胞凋亡和自噬调节剂。我们首先表征了粗提物对多种细胞系的抗增殖活性。使用表达绿色荧光蛋白-微管相关蛋白1轻链3(GFP-LC3)的人宫颈癌细胞系(HeLa细胞)来检测粗提物对自噬的影响。通过对人肺癌细胞系(A549细胞)和HeLa细胞进行蛋白质免疫印迹法(Western blot)证实了它们的活性。通过生物活性导向分级分离,我们发现来自多花山竹子的两种笼状异戊烯基氧杂蒽酮,新藤黄双黄酮和异藤黄双黄酮,可显著诱导细胞凋亡并抑制自噬。我们的结果表明,不同的藤黄属植物对不同的癌细胞系表现出不同程度的毒性。此外,使用高内涵筛选分析来筛选天然产物是鉴定新型自噬调节剂的重要方法。

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