东北红豆杉（Taxus cuspidata）中四种紫杉烷类化合物抑制妇科肿瘤细胞增殖活性研究及其作用机制的初步探讨

天然产物研究与开发 ›› 2010, Vol. 23 ›› Issue (6): 1109-1113.

• 开发研究 • 上一篇

东北红豆杉（Taxus cuspidata）中四种紫杉烷类化合物抑制妇科肿瘤细胞增殖活性研究及其作用机制的初步探讨

李珊¹，马如飞²，王思明³，张嫚丽³，王于方³，董玫²，史清文^3*，张红真^1*

¹河北医科大学第一附属医院妇产科，石家庄 050031；²河北医科大学法医学系河北省法医学重点实验室，石家庄 050017；³河北医科大学药学院，石家庄 050017

收稿日期:2009-05-14 出版日期:2011-01-10 发布日期:2011-10-19
通讯作者: meidong@hebmu.edu.cn
基金资助:
国家自然科学基金（8107255）

Anti-proliferation Activity against Tumor Cells of Non-paclitaxel-type Taxoids from Taxus cuspidate and Its Mechanism

LI Shan¹, MA Ru-fei², WANG Si-ming³, ZHANG Man-li³, WANG Yu-fang³, DONG Mei², SHI Qing-wen^3*, ZHANG Hong-zhen^1*

¹The First Affiliated Hospital of Hebei Medical Uninversity, Shijiazhuang 050031, China；²Department of Forensic Medicine, Hebei Medical Univercity, Shijiazhuang 050017,China；³Department of Medicinal Natural Product Chemistry, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, China

Received:2009-05-14 Online:2011-01-10 Published:2011-10-19

摘要/Abstract

摘要：

通过四唑盐（MTT）比色法检测东北红豆杉中四种紫杉烷类化合物对人子宫颈癌细胞、人子宫内膜癌细胞、人卵巢透明癌细胞和人卵巢囊腺癌细胞增殖的影响，不仅探讨了这些化合物作用的构效关系，还初步探讨了其抑制肿瘤细胞增殖的作用机制。结果发现9,10-去乙酰紫杉宁对人子宫颈癌细胞、人子宫内膜癌细胞和人卵巢囊腺癌细胞的增殖均有明显的抑制作用，与紫杉宁和1β-羟基紫杉宁即使在100 μmol/L的高浓度下，对五种妇科肿瘤细胞的增殖不显示抑制活性；流式细胞学检查发现9,10-去乙酰紫杉宁作用后的HeLa细胞出现凋亡现象。因此推测：1. C-9,10位的羟基和C-5位的肉桂酰基侧链是该类化合物抑制肿瘤细胞增殖所必需的； 2. 9,10-去乙酰紫杉宁有可能是通过诱导肿瘤细胞凋亡来实现其抑制HeLa细胞的增殖作用。

关键词: 东北红豆杉, 紫杉烷类化合物, 肿瘤细胞, 增殖活性, 细胞凋亡

Abstract:

Four non-paclitaxel-type taxoids taxuspine (1), taxinine (2), 1β-hydroxyl-taxinine (3), and 9,10-deacetyl taxinine (4) were isolated from Taxus cuspidata. Their anti-proliferation effects on the cell lines of HeLa, HEC-1, SHIN3, HOC-21, and HAC-2 were evaluated by using MTT assay. In addition, the structure activity relationship and the possible mechanism were discussed. The results showed that only compound 4 exhibited significant anti-proliferation activities against HeLa, HEC-1, and HAC-2 cell lines and 9,10-hydroxyl and 5-cinnamoyl group were essential for the activity. Furthermore, the apoptosis induced by 9 in Hela cell was studied by Flow Cytometry (FCM), which indicated that the anti-proliferation activity of 9,10-deacetyl taxinine was achieved by inducing HeLa cell apoptosis probably.

Key words: Taxus cuspidata, non-paclitaxel-type taxoids, human tumor cell lines, anti-proliferation activity, apoptosis

李珊，马如飞，王思明，张嫚丽，王于方，董玫，史清文，张红真. 东北红豆杉（Taxus cuspidata）中四种紫杉烷类化合物抑制妇科肿瘤细胞增殖活性研究及其作用机制的初步探讨[J]. 天然产物研究与开发, 2010, 23(6): 1109-1113.

LI Shan, MA Ru-Fei, WANG Si-Ming, Zhang-Man-Li, WANG Yu-Fang, Dong-Mei, SHI Qing-Wen, Zhang-Hong-Zhen. Anti-proliferation Activity against Tumor Cells of Non-paclitaxel-type Taxoids from Taxus cuspidate and Its Mechanism[J]. NATURAL PRODUCT RESEARCH AND DEVELOPMENT, 2010, 23(6): 1109-1113.

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东北红豆杉（Taxus cuspidata）中四种紫杉烷类化合物抑制妇科肿瘤细胞增殖活性研究及其作用机制的初步探讨

Anti-proliferation Activity against Tumor Cells of Non-paclitaxel-type Taxoids from Taxus cuspidate and Its Mechanism

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