期刊
TOXICOLOGY LETTERS
卷 215, 期 3, 页码 174-180出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2012.10.015
关键词
Columbamine; Neovascularization; Vasculogenic mimicry; Osteosarcoma; U2OS; Toxicity
类别
资金
- National Natural Science Foundation of China [30971138]
- Chinese Academy of Science Special National Strategic Leader Project [XDA01040200]
- Suzhou City Scientific Research Funds [SS201004, SS201138]
- priority academic program development of Jiangsu Higher Education Institutions (PAPD)
- State Key Laboratory of Stem Cell and Biomaterials built by the Ministry of Science and Technology and Jiangsu Province
- Jiangsu Province's Key Discipline of Medicine [XK201118]
Osteosarcoma is one of the most common malignant bone tumors in children and adolescents. Although extensive efforts have been made in anti-osteosarcoma therapy in recent decades, there are no effective low-toxicity drugs for treating patients with metastatic osteosarcoma. Hence, potent anti-metastatic osteosarcoma drugs are highly desired. In this study, we explored novel small molecular anti-metastatic osteosarcoma agents and found that columbamine (COL), an active component of the herb Coptis chinensis, inhibited the proliferation and neovascularization of metastatic osteosarcoma U2OS cells. COL effectively suppressed U2OS cell proliferation in vitro with an IC50 of 21.31 +/- 0.38 mu M, with low cytotoxicity. Mechanistic studies revealed that COL induces cell cycle arrest at the G2/M transition, which is associated with attenuating CDK6 gene expression and diminishing STAT3 phosphorylation. COL did not significantly promote U2OS cell apoptosis at any of the dosages tested. Additionally, COL inhibited U2OS cell-mediated neovascularization, which was accompanied by the down-regulation of matrix metalloproteinase (MMP) 2 expression and reduction of cell migration, adhesion, and invasion. Taken together, our data show that COL exerts anti-proliferative and anti-vasculogenic effects on metastatic human osteosarcoma U2OS cells with low toxicity. These results warrant further investigation of COL as a potential anti-osteosarcoma and anti-cancer drug. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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