Berberine, a natural compound, suppresses Hedgehog signaling pathway activity and cancer growth

BMC Cancer

Research Article

Ning Ding¹  Jun Yang²  Wenfu Tan²  Yuanqiu Peng²  Yuan Liu²  Juan Wang² 

[1] Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Rd, 201203, Shanghai, P.R. China;State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China;Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, 201203, Shanghai, P.R. China;

关键词: PGE2;    Medulloblastoma;    Berberine;    Cyclopamine;    Medulloblastoma Cell;   

DOI  :  10.1186/s12885-015-1596-z

 received in 2015-02-05, accepted in 2015-08-10,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundBerberine (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.MethodsThe 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.ResultsIn 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-α (TNF-α) 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.ConclusionCollectively, 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.

【 授权许可】

CC BY   
© Wang et al. 2015