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The novel benzimidazole derivative, MPTB, induces cell apoptosis in human chondrosarcoma cells
Author(s) -
Li TeMao,
Lin TsangYu,
Hsu ShengFeng,
Wu ChiMing,
Su YiChang,
Kao ShungTe,
Chang ChihShiang,
Fong YiChin,
Tang ChihHsin
Publication year - 2011
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20749
Subject(s) - calpain , chondrosarcoma , apoptosis , biology , cell culture , cancer research , downregulation and upregulation , gene knockdown , cell , pathology , biochemistry , enzyme , genetics , medicine , gene
Chondrosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. This study is the first to investigate the anti‐cancer effects of the new benzimidazole derivative (5‐methyl‐2(pyridine‐3‐yl)‐1‐(3,4,5‐trimethoxybenzyl)benzimidazole; MPTB) in human chondrosarcoma cells. MPTB‐induced cell apoptosis in two human chondrosarcoma cell lines, JJ012 and SW1353 but not in primary chondrocytes. MPTB‐induced upregulation of Bax and Bak and dysfunction of mitochondria in chondrosarcoma. MPTB triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosol calcium levels, and increased glucose‐regulated protein (GRP) expression. MPTB also increased calpain expression. Transfection of cells with GRP78 or calpain siRNA reduced MPTB‐mediated cell apoptosis in JJ012 cells. Importantly, animal studies have revealed a dramatic 44% reduction in tumor volume after 21 d of treatment. This study demonstrates novel anti‐cancer activity of MPTB against human chondrosarcoma cells and in murine tumor models. Mol. Carcinog. ©2011 Wiley‐Liss, Inc.