A novel benzofuran derivative, ACDB, induces apoptosis of human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress
Metrics: PDF 746 views | HTML 990 views | ?
Chen-Ming Su1,2, Chien-Yu Chen3, Tingting Lu1, Yi Sun1, Weimin Li4, Yuan-Li Huang5, Chun-Hao Tsai6,7, Chih-Shiang Chang3, Chih-Hsin Tang2,5,8
1Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
2Graduate Institute of Basic Medical Science, China Medical University, Taichung Taiwan
3Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan
4Department of Cardiology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
5Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
6School of Medicine, China Medical University, Taichung, Taiwan
7Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
8Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
Chih-Shiang Chang, email: email@example.com
Chih-Hsin, Tang, email: firstname.lastname@example.org
Keywords: benzofuran, chondrosarcoma, apoptosis, endoplasmic reticulum (ER) stress, mitochondrial dysfunction
Received: August 25, 2016 Accepted: October 19, 2016 Published: November 07, 2016
Chondrosarcoma is one of the bone tumor with high mortality in respond to poor radiation and chemotherapy treatment. Here, we analyze the antitumor activity of a novel benzofuran derivative, 2-amino-3-(2-chlorophenyl)-6-(4-dimethylaminophenyl)benzofuran-4-yl acetate (ACDB), in human chondrosarcoma cells. ACDB increased the cell apoptosis of human chondrosarcomas without harm in chondrocytes. ACDB also enhanced endoplasmic reticulum (ER) stress, which was characterized by varieties in the cytosolic calcium levels and induced the expression of glucose-regulated protein (GRP) and calpain. Furthermore, the ACDB-induced chondrosarcoma apoptosis was associated with the upregulation of the B cell lymphoma-2 (Bcl-2) family members including pro- and anti-apoptotic proteins, downregulation of dysfunctional mitochondria that released cytochrome C, and subsequent activation of caspases-3. In addition, the ACDB-mediated cellular apoptosis was suppressed by transfecting cells with glucose-regulated protein (GRP) and calpain siRNA or treating cells with ER stress chelators and caspase inhibitors. Interestingly, animal experiments illustrated a reduction in the tumor volume following ACDB treatment. Together, these results suggest that ACDB may be a novel tumor suppressor of chondrosarcoma, and this study demonstrates that the novel antitumor agent, ACDB, induced apoptosis by mitochondrial dysfunction and ER stress in human chondrosarcoma cells in vitro and in vivo.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.