BL-038, a Benzofuran Derivative, Induces Cell Apoptosis in Human Chondrosarcoma Cells through Reactive Oxygen Species/Mitochondrial Dysfunction and the Caspases Dependent Pathway.
Chondrosarcoma is a highly malignant cartilage-forming bone tumor that has the capacity to invade locally and cause distant metastasis. Moreover, chondrosarcoma is intrinsically resistant to conventional chemotherapy or radiotherapy. The novel benzofuran derivative, BL-038 (2-amino-3-(2,6-dichlorophenyl)-6-(4-methoxyphenyl)benzofuran-4-yl acetate), has been evaluated for its anticancer effects in human chondrosarcoma cells. BL-038 caused cell apoptosis in two human chondrosarcoma cell lines, JJ012 and SW1353, but not in primary chondrocytes. Treatment of chondrosarcoma with BL-038 also induced reactive oxygen species (ROS) production. Furthermore, BL-038 decreased mitochondrial membrane potential (MMP) and changed mitochondrial-related apoptosis, by downregulating the anti-apoptotic activity members (Bcl-2, Bcl-xL) and upregulating pro-apoptotic members (Bax, Bak) of the B-cell lymphoma 2 (Bcl-2) family of proteins, key regulators of the apoptotic machinery in cells. These results demonstrate that in human chondrosarcoma cells, the apoptotic and cytotoxic effects of BL-038 are mediated by the intrinsic mitochondria-mediated apoptotic pathway, which in turn causes the release of cytochrome c, the activation of caspase-9 and caspase-3, and the cleavage of poly (ADP-ribose) polymerase (PARP), to elicit apoptosis response. Our results show that the benzofuran derivative BL-038 induces apoptosis in chondrosarcoma cells.
Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan. anti0822@hotmail.com.
Ju-Fang
JF
Liu
School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan. qaz90006@yahoo.com.tw.
Chien-Yu
CY
Chen
Department of Orthopedic Surgery, China Medical University Hospital, Taichung 404, Taiwan. bonekid1@gmail.com.|School of Chinese Medicine, China Medical University, Taichung 404, Taiwan. bonekid1@gmail.com.
Hsien-Te
HT
Chen
School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan. chihshiang3@gmail.com.
Chih-Shiang
CS
Chang
Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan. chtang@mail.cmu.edu.tw.|Department of Pharmacology, School of Medicine, China Medical University, Taichung 404, Taiwan. chtang@mail.cmu.edu.tw.|Department of Biotechnology, College of Health Science, Asia University, Taichung 413, Taiwan. chtang@mail.cmu.edu.tw.
Chih-Hsin
CH
Tang
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002813:Chondrosarcoma / Q000378:metabolism / Q000473:pathology; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000616435:BL-038; D001572:Benzofurans; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases
ROS; apoptosis; benzofuran derivative; chondrosarcoma