Benzobijuglone, a novel cytotoxic compound from Juglans mandshurica, induced apoptosis in HeLa cervical cancer cells

Benzobijuglone, a novel cytotoxic compound from Juglans mandshurica, induced apoptosis in HeLa cervical cancer cells
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DOI:
10.1016/j.phymed.2007.09.004
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发表时间:
2007-12-01
期刊:
影响因子:
7.9
通讯作者:
Bao, Yong-Ming
Bao, Yong-Ming
中科院分区:
医学1区
文献类型:
--
作者:
Li, Zhi-Bo;Wang, Jing-Yun;Bao, Yong-Ming

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从胡桃楸中分离得到一个新的醌类化合物对羟基甲氧基苯并二胡桃醌(HMBBJ),该化合物对HeLa细胞具有细胞毒活性。其化学结构经核磁共振谱和高分辨离子迁移谱确定。本文首次研究了其诱导HeLa细胞凋亡的能力。HMBBJ处理后,HeLa细胞生长受到抑制,细胞呈现典型的凋亡形态学特征。流式细胞仪分析结果显示,HMBBJ可使HeLa细胞周期阻滞于G2/M期,并呈剂量依赖性地增加HeLa细胞的凋亡率。同时,HMBBJ可增加caspase-8、-3和Bax的表达,降低Bcl-2的表达,降低Δ psi(m)。这些结果表明,HMBBJ可通过线粒体依赖性途径和激活caspase级联反应诱导HeLa细胞凋亡,可能是一种潜在的肿瘤治疗药物。(c)2007年,Elsevier GmbH。All rights reserved.
A new quinone compound, p-hydroxymethoxybenzobijuglone (HMBBJ), isolated from Juglans mandshurica by bioassay-guided fractionation, showed cytotoxic activity against HeLa cell line. Its chemical structure was determined by NMR and HREIMS spectra. In this paper, its ability to induce apoptosis in HeLa cells was studied for the first time. After treated with HMBBJ, the growth of HeLa cells was inhibited and cells displayed typical morphological apoptotic characteristics. Data from flow cytometry analysis showed that the HeLa cell cycle was arrested in the G2/M phase by HMBBJ, and the apoptotic rate of HeLa cells increased in a dose-dependent manner. Meanwhile, HMBBJ increased the expression of caspase-8, -3 and Bax, decreased the expression of Bcl-2, and lowered the Delta psi(m). These findings reveal that HMBBJ could efficiently induce HeLa cells apoptosis through mitochondria dependent pathway and activation of the caspase cascade, and it may be a potential chemotherapeutic candidate for the treatment of cancer. (c) 2007 Elsevier GmbH. All rights reserved.