title: 1-benzyl-2-phenylbenzimidazole (BPB), a benzimidazole derivative, induces cell apoptosis in human chondrosarcoma through intrinsic and extrinsic pathways.
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.
authors.affiliation: Central Laboratory, Shin Kong Wu Ho-Su Memorial Hospital, No.95, Wunchang Road, Shihlin District, Taipei City 111, Taiwan. chtang@mail.cmu.edu.tw.
authors.forename: Ju-Fang
authors.initials: JF
authors.lastname: Liu
authors.forename: Yuan-Li
authors.initials: YL
authors.lastname: Huang
authors.forename: Wei-Hung
authors.initials: WH
authors.lastname: Yang
authors.forename: Chih-Shiang
authors.initials: CS
authors.lastname: Chang
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000473:pathology*; D002478:Cells, Cultured; D002813:Chondrosarcoma / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C000600795:1-benzyl-2-phenylbenzimidazole; D000970:Antineoplastic Agents; D001562:Benzimidazoles; C117755:2-phenylbenzimidazole