title: Unraveling the novel anti-osteosarcoma function of coptisine and its mechanisms.
abstract: Uncontrolled cell proliferation and robust angiogenesis play critical roles in osteosarcoma growth and metastasis. In this study we explored novel agents derived from traditional Chinese medicinal herbs that potently inhibit osteosarcoma growth and metastasis. Coptisine, an active component of the herb Coptidis rhizoma, markedly inhibited aggressive osteosarcoma cell proliferation. Coptisine induced cell cycle arrest at the G0/G1 phase through downregulation of CDK4 and cyclin D1 expression and effectively suppressed tumor growth in a xenografted mouse model. Coptisine significantly impeded osteosarcoma cell migration, invasion, and capillary-like network formation by decreasing the expression of VE-cadherin and integrin ß3, and diminishing STAT3 phosphorylation. Coptisine significantly elevated blood erythrocyte and hemoglobin levels while still remaining within the normal range. It also moderately increased white blood cell and platelet counts. These data suggest that coptisine exerts a strong anti-osteosarcoma effect with very low toxicity and is a potential anti-osteosarcoma drug candidate.
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: Di
authors.initials: D
authors.lastname: Yu
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: Shilong
authors.initials: S
authors.lastname: Fu
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: Zhifei
authors.initials: Z
authors.lastname: Cao
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.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: Gaochuan
authors.initials: G
authors.lastname: Zhang
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: Yanyan
authors.initials: Y
authors.lastname: Pan
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: Wenming
authors.initials: W
authors.lastname: Liu
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. Electronic address: quanshengzhou@yahoo.com.
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001859:Bone Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D015820:Cadherins / Q000032:analysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D012516:Osteosarcoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D000972:Antineoplastic Agents, Phytogenic; D001599:Berberine; D015820:Cadherins; D000099152:Cadherin 5; C034384:coptisine
keywords: Angiogenesis; Cancer; Coptisine; Osteosarcoma; Proliferation; Vasculogenic mimicry