Int. J. Mol. Sci. 2012, 13(12), 16472-16488; doi:10.3390/ijms131216472
Article

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

1,2,†email, 3,†email, 4,5,6email, 2email and 7,8,* email
Received: 22 October 2012; in revised form: 23 November 2012 / Accepted: 27 November 2012 / Published: 4 December 2012
(This article belongs to the collection Programmed Cell Death and Apoptosis)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: 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.
Keywords: chondrosarcoma; benzimidazole; extrinsic pathway; intrinsic pathway; Chinese herb
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MDPI and ACS Style

Liu, J.-F.; Huang, Y.-L.; Yang, W.-H.; Chang, C.-S.; Tang, C.-H. 1-Benzyl-2-Phenylbenzimidazole (BPB), a Benzimidazole Derivative, Induces Cell Apoptosis in Human Chondrosarcoma through Intrinsic and Extrinsic Pathways. Int. J. Mol. Sci. 2012, 13, 16472-16488.

AMA Style

Liu J-F, Huang Y-L, Yang W-H, Chang C-S, Tang C-H. 1-Benzyl-2-Phenylbenzimidazole (BPB), a Benzimidazole Derivative, Induces Cell Apoptosis in Human Chondrosarcoma through Intrinsic and Extrinsic Pathways. International Journal of Molecular Sciences. 2012; 13(12):16472-16488.

Chicago/Turabian Style

Liu, Ju-Fang; Huang, Yuan-Li; Yang, Wei-Hung; Chang, Chih-Shiang; Tang, Chih-Hsin. 2012. "1-Benzyl-2-Phenylbenzimidazole (BPB), a Benzimidazole Derivative, Induces Cell Apoptosis in Human Chondrosarcoma through Intrinsic and Extrinsic Pathways." Int. J. Mol. Sci. 13, no. 12: 16472-16488.


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