CYP3A-mediated apoptosis of dauricine in cultured human bronchial epithelial cells and in lungs of CD-1 mice
文献类型：期刊论文
| 作者 | Jin, Hua2; Shen, Shuijie2; Chen, Xiaoyan1 ; Zhong, Dafang1; Zheng, Jiang2
|
| 刊名 | TOXICOLOGY AND APPLIED PHARMACOLOGY
 |
| 出版日期 | 2012-06-15 |
| 卷号 | 261期号:3页码:248-254 |
| 关键词 | Dauricine GSH depletion Apoptosis CYP3A |
| ISSN号 | 0041-008X |
| DOI | 10.1016/j.taap.2012.03.025 |
| 文献子类 | Article |
| 英文摘要 | Dauricine is the major bioactive component isolated from the root of Menispermum dauricum DC and has shown promising pharmacologic activities with a great potential for clinical use. Recently, we found that intraperitoneal exposure of dauricine produced selective pulmonary injury in mice. A quinone methide metabolite of dauricine was identified and is suggested to be associated with the pulmonary toxicity of dauricine. The present study evaluated the apoptotic effect of dauricine in cultured cells and mice, determined the change in cellular glutathione (GSH) contents after exposure to dauricine, investigated the role of GSH depletion in dauricine-induced cytotoxicity and apoptosis, and examined the role of CYP3A in dauricine-induced GSH depletion and apoptosis. Dauricine was found to induce apoptosis in NL-20 cells. Additionally, intraperitoneal administration of dauricine caused GSH depletion and apoptosis in lungs of mice. Treatment with ketoconazole, an inhibitor of CYP3A, reversed cellular GSH depletion in lungs of mice given dauricine and showed protective effect on dauricine-induced apoptosis in lungs of mice. This indicates that metabolic activation is involved in dauricine-induced GSH-depletion, cytotoxicity and apoptosis. The glutathione depletor L-buthionine sulfoximine showed potentiating effect on cytotoxicity and apoptosis induced by dauricine. We propose that dauricine is metabolized to a quinone methide intermediate which depletes cellular GSH, and the depletion of GSH may trigger and/or intensify the cytotoxicity and apoptosis induced by dauricine. (C) 2012 Elsevier Inc. All rights reserved. |
| WOS关键词 | CANCER CELLS ; IN-VITRO ; BISBENZYLISOQUINOLINE ALKALOIDS ; CYTOTOXIC ACTIVITIES ; TETRANDRINE ; RATS ; PROLIFERATION ; INVOLVEMENT ; HYPOXIA ; PATHWAY |
| 资助项目 | National Natural Science Foundation of China[30873119] |
| WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000305502600003 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278039]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Zheng, Jiang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Univ Washington, Ctr Dev Therapeut, Seattle Childrens Res Inst, Div Gastroenterol & Hepatol,Dept Pediat, Seattle, WA 98101 USA; |
| 推荐引用方式 GB/T 7714 | Jin, Hua,Shen, Shuijie,Chen, Xiaoyan,et al. CYP3A-mediated apoptosis of dauricine in cultured human bronchial epithelial cells and in lungs of CD-1 mice[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2012,261(3):248-254. |
| APA | Jin, Hua,Shen, Shuijie,Chen, Xiaoyan,Zhong, Dafang,&Zheng, Jiang.(2012).CYP3A-mediated apoptosis of dauricine in cultured human bronchial epithelial cells and in lungs of CD-1 mice.TOXICOLOGY AND APPLIED PHARMACOLOGY,261(3),248-254. |
| MLA | Jin, Hua,et al."CYP3A-mediated apoptosis of dauricine in cultured human bronchial epithelial cells and in lungs of CD-1 mice".TOXICOLOGY AND APPLIED PHARMACOLOGY 261.3(2012):248-254. |
入库方式： OAI收割
来源：上海药物研究所
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