Columbamine suppresses the proliferation and neovascularization of metastatic osteosarcoma U2OS cells with low cytotoxicity.

Abstract

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 IC(50) of 21.31±0.38μM, 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.

• Authors: Meimei Bao, Zhifei Cao, Di Yu, Shilong Fu, Gaochuan Zhang, Ping Yang, Yanyan Pan, Bo Yang, Hongyan Han, Quansheng Zhou
• Journal: Toxicology letters (Toxicol Lett) Vol. 215 Issue 3 Pg. 174-80 (Dec 17 2012) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 23124089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Berberine Alkaloids
• Plant Extracts
• columbamine

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Berberine Alkaloids (chemistry, pharmacology, therapeutic use)
• Bone Neoplasms (blood supply, drug therapy, pathology)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Humans
• Molecular Structure
• Neoplasm Invasiveness
• Neovascularization, Pathologic (drug therapy)
• Osteosarcoma (blood supply, drug therapy, pathology)
• Plant Extracts (chemistry, pharmacology, therapeutic use)