Berberine, a natural compound, suppresses Hedgehog signaling pathway activity and cancer growth
文献类型：期刊论文
| 作者 | Wang, Juan1; Peng, Yuanqiu1; Liu, Yuan1; Yang, Jun1; Ding, Ning2,3; Tan, Wenfu1 |
| 刊名 | BMC CANCER
 |
| 出版日期 | 2015-08-22 |
| 卷号 | 15 |
| ISSN号 | 1471-2407 |
| DOI | 10.1186/s12885-015-1596-z |
| 文献子类 | Article |
| 英文摘要 | Background: Berberine (BBR), a natural alkaloid compound, is used as a non-prescription drug in China for treating diarrhea and gastroenteritis. Many studies have revealed that BBR possesses anticancer effect. However, the molecular mechanisms underlying its anticancer action is far from being fully elucidated. This study is aimed to determine the effect of BBR on the hedgehog (Hh) activity and the growth of cancers addiction to Hh activity. Methods: The Hh activity was determined by dual luciferase assays and quantitative RT-PCR analyses. The growth inhibition of BBR on medulloblastoma which was obtained from ptch+/-; p53-/- mice was analyzed by 5- bromo-2-deoxyuridine (Brdu) assays and by allografting the medulloblastoma into nude mice. The data were statistically analyzed by one-way analysis of variance (ANOVA), and multiple comparison between the groups was performed using Dunnett's method. Results: In this study, we found that BBR significantly inhibited the Hh pathway activity. Meanwhile, we observed that BBR failed to affect the transcriptional factors activities provoked by tumor necrosis factor-alpha (TNF-alpha) and Prostaglandin E2 (PGE2), thus suggesting its unique property against Hh pathway activity. Further studies revealed that BBR inhibited the Hh pathway activity by potentially targeting the critical component Smoothened (Smo) and most likely shared the same binding site on Smo with cyclopamine, a classical Smo inhibitor. Finally, we demonstrated that BBR obviously suppressed the Hh-dependent medulloblastoma growth in vitro and in vivo. Conclusion: Collectively, our study uncovered a novel molecular mechanism responsible for the anticancer action of BBR, thus opening the way for the usage of BBR for therapeutics of cancers addiction to aberrant Hh pathway activity. |
| WOS关键词 | SMALL-MOLECULE ANTAGONISTS ; BREAST-CANCER ; INHIBITION ; CELLS ; MECHANISMS ; APOPTOSIS ; MICE ; GLI ; MEDULLOBLASTOMA ; TRANSCRIPTION |
| 资助项目 | National Natural Science Foundation of China[81573452] ; Shanghai Municipal Science & Technology Pillar Program for Bio-pharmaceuticals[14431900400] ; State Key Laboratory of Drug Research[SIMM1501KF-09] ; State Key Laboratory of Drug Research[SIMM1403KF-08] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000359838500001 |
| 出版者 | BIOMED CENTRAL LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276434]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Tan, Wenfu |
| 作者单位 | 1.Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 201203, Peoples R China; 2.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Juan,Peng, Yuanqiu,Liu, Yuan,et al. Berberine, a natural compound, suppresses Hedgehog signaling pathway activity and cancer growth[J]. BMC CANCER,2015,15. |
| APA | Wang, Juan,Peng, Yuanqiu,Liu, Yuan,Yang, Jun,Ding, Ning,&Tan, Wenfu.(2015).Berberine, a natural compound, suppresses Hedgehog signaling pathway activity and cancer growth.BMC CANCER,15. |
| MLA | Wang, Juan,et al."Berberine, a natural compound, suppresses Hedgehog signaling pathway activity and cancer growth".BMC CANCER 15(2015). |
入库方式： OAI收割
来源：上海药物研究所
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