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BFPP, a phloroglucinol derivative, induces cell apoptosis in human chondrosarcoma cells through endoplasmic reticulum stress |
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| Authors: | Ju-Fang Liu Yi-Chin Fong Sheng-Chu Kuo Chih-Hsin Tang |
| Affiliation: | a Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan b School of Chinese Medicine, China Medical University, Taichung, Taiwan c Department of Orthopaedics, China Medical University Beigang Hospital, Yun-Lin County, Taiwan d Department of Orthopaedics, China Medical University Hospital, Taichung, Taiwan e Department of Pharmacology, China Medical University, Taichung, Taiwan f Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan |
| Abstract: | Chondrosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. This study is the first to investigate the anticancer effects of the new phloroglucinol derivative (2,4-bis(2-fluorophenylacetyl)phloroglucinol; BFPP) in human chondrosarcoma cells. BFPP induced cell apoptosis in two human chondrosarcoma cell lines, JJ012 and SW1353 but not in primary chondrocytes. BFPP triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosol calcium levels, and increased glucose-regulated protein 78 (GRP78) expression, but failed to show the same effects on GRP94 expression. BFPP also increased calpain expression and activity. Transfection of cells with GRP78 or calpain siRNA reduced BFPP-mediated cell apoptosis in JJ012 cells. Importantly, animal studies have revealed a dramatic 50% reduction in tumor volume after 21 days of treatment. This study demonstrates novel anticancer activity of BFPP against human chondrosarcoma cells and in murine tumor models. |
| Keywords: | BFPP Chondrosarcoma ER GRP78 Calpain |
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