TY - JOUR
T1 - 1-Benzyl-2-Phenylbenzimidazole (BPB), a Benzimidazole derivative, induces cell apoptosis in human chondrosarcoma through intrinsic and extrinsic pathways
AU - Liu, Ju Fang
AU - Huang, Yuan Li
AU - Yang, Wei Hung
AU - Chang, Chih Shiang
AU - Tang, Chih Hsin
PY - 2012/12/1
Y1 - 2012/12/1
N2 - 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.
AB - 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.
KW - Benzimidazole
KW - Chinese herb
KW - Chondrosarcoma
KW - Extrinsic pathway
KW - Intrinsic pathway
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UR - http://www.scopus.com/inward/citedby.url?scp=84871708931&partnerID=8YFLogxK
U2 - 10.3390/ijms131216472
DO - 10.3390/ijms131216472
M3 - Article
C2 - 23211670
AN - SCOPUS:84871708931
VL - 13
SP - 16472
EP - 16488
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 12
ER -