title: Plumbagin induces apoptosis via the p53 pathway and generation of reactive             oxygen species in human osteosarcoma cells.
abstract: Osteosarcoma, which is the most common primary bone tumor, occurs most frequently in adolescents. A number of studies have indicated that plumbagin (PL) (5-hydroxy-2-methyl-1, 4-naphthoquinone), a compound found in the plants of the Plumbaginaceae and Droseraceae families, possesses anticancer activity. However, its anticancer effects and mechanisms against osteosarcoma have not been explored. To determine the anticancer effect of PL on osteosarcoma cell lines MG-63 and U2OS, cell viability, apoptosis, cell cycle distribution, caspase-3 and caspase-9 activity and intracellular reactive oxygen species (ROS) generation were measured, and Western blot analyses were performed. PL significantly inhibited the growth of osteosarcoma cells, particularly U2OS cells. PL up-regulated the expression of p53 in U2OS cells and p21 in the two osteosarcoma cell lines causing cell cycle arrest by decreasing the expression of murine double minute 2 (MDM2)/cyclin B1 and cyclin D1. Furthermore, PL altered the ratio of Bax/Bcl-2, and may have triggered the mitochondrial apoptotic pathway, resulting in caspase-3 and caspase-9 activation. We also found that PL induced the generation of ROS in osteosarcoma cell lines. To conclude, PL exerted anticancer activity on osteosarcoma cells by inducing pro-apoptotic signaling and modulating the intracellular ROS that causes induction of apoptosis. These effects may relate to the p53 status.
authors: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors: Linqiang
authors: L
authors: Tian
authors: Delong
authors: D
authors: Yin
authors: Ye
authors: Y
authors: Ren
authors: Chen
authors: C
authors: Gong
authors: Anmin
authors: A
authors: Chen
authors: Feng-Jin
authors: FJ
authors: Guo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D006801:Humans; D009285:Naphthoquinones / Q000494:pharmacology*; D012516:Osteosarcoma / Q000473:pathology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D053148:Caspase 3; D053453:Caspase 9; C014758:plumbagin