1-Benzyl-2-Phenylbenzimidazole (BPB), a Benzimidazole Derivative, Induces Cell Apoptosis in Human Chondrosarcoma through Intrinsic and Extrinsic Pathways

International Journal of Molecular Sciences

Ju-Fang Liu³  Yuan-Li Huang⁴  Wei-Hung Yang²  Chih-Shiang Chang¹ 

[1] Graduate Institute of Pharmaceutical Chemistry, China Medical University, No.91 Hsueh-Shih Road, Taichung 40402, Taiwan; E-Mail:;Department of Orthopedic Surgery, Taichung Hospital, Department of Health, No.199, Sec. 1, San-Min Road, Taichung 402, Taiwan; E-Mail:;Central Laboratory, Shin Kong Wu Ho-Su Memorial Hospital, No.95, Wunchang Road, Shihlin District, Taipei City 111, Taiwan; E-Mail:;Department of Biotechnology, College of Health Science, Asia University, No.500, Lioufeng Road, Wufeng, Taichung 41354, Taiwan; E-Mail:

关键词: chondrosarcoma;    benzimidazole;    extrinsic pathway;    intrinsic pathway;    Chinese herb;   

DOI  :  10.3390/ijms131216472

来源: mdpi

【 摘 要 】

In this study, we investigated the anticancer effects of a new benzimidazole derivative, 1-benzyl-2-phenyl -benzimidazole (BPB), in human chondrosarcoma cells. BPB-mediated apoptosis was assessed by the MTT assay and flow cytometry analysis. The in vivo efficacy was examined in a JJ012 xenograft model. Here we found that BPB induced apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353) but not in primary chondrocytes. BPB induced upregulation of Bax, Bad and Bak, downregulation of Bcl-2, Bid and Bcl-XL and dysfunction of mitochondria in chondrosarcoma. In addition, BPB also promoted cytosolic releases AIF and Endo G. Furthermore, it triggered extrinsic death receptor-dependent pathway, which was characterized by activating Fas, FADD and caspase-8. Most importantly, animal studies revealed a dramatic 40% reduction in tumor volume after 21 days of treatment. Thus, BPB may be a novel anticancer agent for the treatment of chondrosarcoma.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.