title: Bufalin induces apoptosis in the U‑2OS human osteosarcoma cell line via triggering the mitochondrial pathway.
abstract: Bufalin has been shown to induce apoptosis in osteosarcoma cells; however, the underlying mechanism has not been elucidated. The purpose of the present study was to investigate whether mitochondria‑mediated signaling pathways trigger the process of apoptosis in the U‑2OS osteosarcoma cell line. Bufalin inhibited the proliferation and induced apoptosis in U‑2OS cells in a time- and dose‑dependent manner. Bufalin‑induced apoptosis was accompanied with a significant reduction of the mitochondrial membrane potential, release of mitochondrial cytochrome c into the cytosol, activation of caspase‑3, caspase‑9 and poly(adenosine diphosphate ribose) polymerase, as well as downregulation of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein. Cyclosporin A, a specific inhibitor of the mitochondrial permeability transition pore, attenuated bufalin-induced apoptosis. In conclusion, the present study revealed that bufalin induced apoptosis in the U‑2OS human osteosarcoma cell line via triggering of the mitochondrial pathway.
authors.affiliation: Department of Pharmacy, People's Hospital of Zhangqiu, Shandong 250200, P.R. China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, People's Hospital of Zhangqiu, Shandong 250200, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, People's Hospital of Zhangqiu, Shandong 250200, P.R. China.
authors.forename: Zhongji
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, People's Hospital of Zhangqiu, Shandong 250200, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: Department of Orthopaedic Surgery, People's Hospital of Zhangqiu, Shandong 250200, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Spinal Department of Orthopaedic Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002018:Bufanolides / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D012516:Osteosarcoma / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002018:Bufanolides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016572:Cyclosporine; C022777:bufalin