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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.
AuthorsDi Yu, Shilong Fu, Zhifei Cao, Meimei Bao, Gaochuan Zhang, Yanyan Pan, Wenming Liu, Quansheng Zhou
JournalToxicology letters (Toxicol Lett) Vol. 226 Issue 3 Pg. 328-36 (May 02 2014) ISSN: 1879-3169 [Electronic] Netherlands
PMID24607417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014. Published by Elsevier Ireland Ltd.
Chemical References
  • Antigens, CD
  • Antineoplastic Agents, Phytogenic
  • Cadherins
  • cadherin 5
  • coptisine
  • Berberine
Topics
  • Animals
  • Antigens, CD (analysis)
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Berberine (analogs & derivatives, pharmacology)
  • Bone Neoplasms (blood supply, drug therapy, pathology)
  • Cadherins (analysis)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic (prevention & control)
  • Osteosarcoma (blood supply, drug therapy, pathology)

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