Reversal of P-gp and MRP1-mediated multidrug resistance by H6, a gypenoside aglycon from Gynostemma pentaphyllum, in vincristine-resistant human oral cancer (KB/VCR) cells
文献类型：期刊论文
| 作者 | Zhu, Hengrui1; Liu, Zulong1; Tang, Lisha1; Liu, Junhua2; Zhou, Mei1; Xie, Fang1; Wang, Zheng1; Wang, Yuqi1; Shen, Sida2; Hu, Lihong2 |
| 刊名 | EUROPEAN JOURNAL OF PHARMACOLOGY
 |
| 出版日期 | 2012-12-05 |
| 卷号 | 696期号:1-3页码:43-53 |
| ISSN号 | 0014-2999 |
| 关键词 | Gypenoside aglycon Gynostemma pentaphyllum Multidrug resistance (MDR) KB/VCR cells P-glycoprotein (P-gp) Multidrug resistance associated protein 1 (MRP1) |
| DOI | 10.1016/j.ejphar.2012.09.046 |
| 文献子类 | Article |
| 英文摘要 | Multidrug resistance (MDR) to anticancer drugs is a major obstacle to successful chemotherapy in the treatment of cancers. Identification of natural compounds capable of circumventing MDR with minimal adverse side effects is an attractive goal. Here, we found that H6, a gypenoside aglycon from Gynostemma pentaphyllum, displayed potent anti-MDR activity. Average resistant fold (RF) of H6 is 1.03 and 1.04 in KB/VCR and MCF-7/ADR cells compared to their parental cells. H6 alone ranging from 2 mu mol/l to 40 mu mol/l (mu M) did not display a significant anti-proliferative effect on KB/VCR cells and other cells, while the compound at these concentrations enhanced the cytotoxicity of vincristine (VCR) to KB/VCR cells. H6 showed a significant synergistic effect in combination with VCR. By quantification of sub-G(1) fraction cells, H6 also enhanced the VCR-induced apoptosis in a dose-dependent manner. The short time treatment with H6 increased the intracellular accumulation of rhodamine 123 (Rho123) and 5(6)-carboxyfluorescein diacetate (CFDA) in KB/VCR cells. Further studies showed that H6 treatment resulted in the decrease of the RNA transcript level of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP). H6 inhibited the function of P-gp by stimulating P-gp ATPase activity and decreased MRP1 expression with a blockade of STAT3 phosphorylation. These findings suggest that H6, a multi-targets reversal agent with no significant toxic effect, may be a potential candidate to circumvent the P-gp and MRP1-mediated MDR. (C) 2012 Elsevier B.V. All rights reserved. |
| WOS关键词 | ACUTE MYELOID-LEUKEMIA ; ABC-TRANSPORTERS ; GLYCOPROTEIN INHIBITORS ; FLOW-CYTOMETRY ; IN-VITRO ; EXPRESSION ; MRP1 ; PROTEIN ; CHEMOTHERAPY ; MECHANISMS |
| 资助项目 | China Postdoctoral Science Foundation[2011M500066] ; National Natural Science Foundation of China[30925040] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | ELSEVIER SCIENCE BV |
| WOS记录号 | WOS:000310582100007 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277850]  |
| 专题 | 上海中药现代化研究中心 |
| 通讯作者 | Liu, Zulong |
| 作者单位 | 1.Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Inst Genet, Shanghai 200433, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Res Ctr Modernizat Tradit Chinese Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhu, Hengrui,Liu, Zulong,Tang, Lisha,et al. Reversal of P-gp and MRP1-mediated multidrug resistance by H6, a gypenoside aglycon from Gynostemma pentaphyllum, in vincristine-resistant human oral cancer (KB/VCR) cells[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2012,696(1-3):43-53. |
| APA | Zhu, Hengrui.,Liu, Zulong.,Tang, Lisha.,Liu, Junhua.,Zhou, Mei.,...&Yu, Long.(2012).Reversal of P-gp and MRP1-mediated multidrug resistance by H6, a gypenoside aglycon from Gynostemma pentaphyllum, in vincristine-resistant human oral cancer (KB/VCR) cells.EUROPEAN JOURNAL OF PHARMACOLOGY,696(1-3),43-53. |
| MLA | Zhu, Hengrui,et al."Reversal of P-gp and MRP1-mediated multidrug resistance by H6, a gypenoside aglycon from Gynostemma pentaphyllum, in vincristine-resistant human oral cancer (KB/VCR) cells".EUROPEAN JOURNAL OF PHARMACOLOGY 696.1-3(2012):43-53. |
入库方式： OAI收割
来源：上海药物研究所
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