title: Bufalin inhibited the growth of human osteosarcoma MG-63 cells via down-regulation of Bcl-2/Bax and triggering of the mitochondrial pathway.
abstract: Cinobufacini (Huachansu), a Chinese medicine prepared from the skin of Bufo bufo gargarizans Cantor (Bufonidae), has potent anti-tumor activity in vitro and in vivo. However, the molecular mechanism of cell apoptosis induced by Bufalin remains elusive. Here, we investigated the apoptosis in Bufalin-treated human osteosarcoma MG-63 cells. The results showed that Bufalin could inhibit cell proliferation and induce apoptosis in a dose- and time-dependent manner. Further investigation revealed that a disruption of mitochondrial transmembrane potential (MMP) and an up-regulation of reactive oxygen species (ROS) in Bufalin-treated cells. By western blot analysis, we found that the up-regulation of Apaf-1, cleaved PARP, cleaved caspase-3, cleaved caspase-9, and Bax/Bcl-2, varies with different concentration of Bufalin. These protein interactions may play a pivotal role in the regulation of apoptosis. Taken together, these results overall indicate that Bufalin could be used as an effective anti-tumor agent in therapy of osteosarcoma targets the mitochondrial-dependent signaling pathway.
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital of Harbin Medical University, No.23 Youzheng street, Harbin, Heilongjiang province, 150001, China.
authors.forename: Dewei
authors.initials: D
authors.lastname: Wang
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Bi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002018:Bufanolides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; D002018:Bufanolides; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C022777:bufalin