title: 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.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Meimei
authors.initials: M
authors.lastname: Bao
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Cao
authors.forename: Di
authors.initials: D
authors.lastname: Yu
authors.forename: Shilong
authors.initials: S
authors.lastname: Fu
authors.forename: Gaochuan
authors.initials: G
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Pan
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Han
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001600:Berberine Alkaloids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012516:Osteosarcoma / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001600:Berberine Alkaloids; D010936:Plant Extracts; C055786:columbamine