BL-038, a Benzofuran Derivative, Induces Cell Apoptosis in Human Chondrosarcoma Cells through Reactive Oxygen Species/Mitochondrial Dysfunction and the Caspases Dependent Pathway

Abstract

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.

Tanshinone IIA inhibits angiogenesis in human endothelial progenitor cells in vitro and in vivo

“…EPCs were treated with or without tanshinone IIA for 24 h, then subjected to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT; 0.5 mg/mL) for 30 min. MTT was dissolved in dimethylsulfoxide (DMSO) and the absorbance was measured at 550 nm using a microplate reader (Bio-Tek, Winooski, VT, USA) [ 25 ].…”

Soya-cerebroside reduces IL-1β-induced MMP-1 production in chondrocytes and inhibits cartilage degradation: implications for the treatment of osteoarthritis

“…Cells were treated with or without soya-cerebroside for 24 or 48 h, then incubated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT; 0.5 mg/mL) for 30 min. MTT was dissolved in dimethylsulfoxide and the absorbance was measured at 550 nm using a microplate reader (Bio-Tek, Winooski, VT, USA) (Lee et al, 2019;Liu, Chen, Chen, Chang, & Tang, 2016).…”

Glucocerebroside reduces endothelial progenitor cell-induced angiogenesis

“…Cells were stimulated with glucocerebroside and then treated with MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] for 30 min. The MTT was dissolved in DMSO and absorbance was detected using a microplate reader (BioTek Instruments, Winooski, VT, USA) (Lee et al, 2019;Liu, Chen, Chen, Chang, & Tang, 2016).…”