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1-benzyl-2-phenylbenzimidazole (BPB), a benzimidazole derivative, induces cell apoptosis in human chondrosarcoma through intrinsic and extrinsic pathways

Liu, Ju-Fang ; Huang, Yuan-Li ; Yang, Wei-Hung ; Chang, Chih-Shiang ; Tang, Chih-Hsin

International journal of molecular sciences, 2012-12, Vol.13 (12), p.16472-16488 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
1-benzyl-2-phenylbenzimidazole (BPB), a benzimidazole derivative, induces cell apoptosis in human chondrosarcoma through intrinsic and extrinsic pathways
Autor: Liu, Ju-Fang ; Huang, Yuan-Li ; Yang, Wei-Hung ; Chang, Chih-Shiang ; Tang, Chih-Hsin
Assuntos: Animals ; Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; benzimidazole ; Benzimidazoles - chemistry ; Benzimidazoles - pharmacology ; Biotechnology ; Bone Neoplasms - pathology ; Bone surgery ; Cancer therapies ; Cell death ; Cells, Cultured ; Chinese herb ; chondrosarcoma ; Chondrosarcoma - pathology ; Cytochrome ; extrinsic pathway ; Humans ; intrinsic pathway ; Male ; Medical prognosis ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mice, SCID ; Mitochondria ; Pharmaceuticals ; Signal Transduction - drug effects ; Xenograft Model Antitumor Assays
É parte de: International journal of molecular sciences, 2012-12, Vol.13 (12), p.16472-16488
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These authors contributed equally to this work.
Descrição: 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.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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1-benzyl-2-phenylbenzimidazole (BPB), a benzimidazole derivative, induces cell apoptosis in human chondrosarcoma through intrinsic and extrinsic pathways

Liu, Ju-Fang ; Huang, Yuan-Li ; Yang, Wei-Hung ; Chang, Chih-Shiang ; Tang, Chih-Hsin

Switzerland: MDPI AG

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