从辽东楤木中分离得到的新型化合物 HY253 通过细胞色素 c 介导的内在途径诱导 HeLa 细胞凋亡。

HY253, a novel compound isolated from Aralia continentalis, induces apoptosis via cytochrome c-mediated intrinsic pathway in HeLa cells.

机构信息

Department of Medical Genetics, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Republic of Korea.

出版信息

Bioorg Med Chem Lett. 2009 Feb 1;19(3):797-9. doi: 10.1016/j.bmcl.2008.12.009. Epub 2008 Dec 7.

DOI:10.1016/j.bmcl.2008.12.009

PMID:19097782

Abstract

This study was aimed to elucidate the novel structure of HY253 isolated from the roots of Aralia continentalis and to evaluate its detailed mechanisms on apoptotic induction in HY253-treated HeLa cells. The structure of HY253 was elucidated based on the interpretation of the NMR spectra, as 7,8a-divinyl-2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol. The TUNEL assay using flow cytometer revealed an appreciable apoptotic induction in HeLa cells treated with 100 microM of HY253 for 48 h. This apoptotic induction is associated with cytochrome c release from mitochondria, via up-regulation of pro-apoptotic Bcl-2 proteins, such as Bax and Bak, which, in turn, resulted in the activation of caspase-8, -9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP).

摘要

本研究旨在阐明从土当归根部分离得到的 HY253 的新结构，并评估其在 HY253 处理的 HeLa 细胞中诱导细胞凋亡的详细机制。通过对 NMR 谱的解释，阐明了 HY253 的结构，确定为 7,8a-二乙烯基-2,4a,4b,5,6,7,8,8a,9,9a-十氢-1H-芴-2,4a,4b,9a-四醇。使用流式细胞仪的 TUNEL 检测显示，100μM 的 HY253 处理 HeLa 细胞 48 小时后可显著诱导细胞凋亡。这种细胞凋亡与细胞色素 c 从线粒体释放有关，通过上调促凋亡的 Bcl-2 蛋白，如 Bax 和 Bak，进而导致 caspase-8、-9 和 -3 的激活，以及多聚（ADP-核糖）聚合酶（PARP）的裂解。