Artemisinin and its analogs, the well-established clinically used anti-malarial traditional medicine, have been proven to have potent anticancer activities. We have demonstrated that Artemisinin and analogs have significant anti-ovarian cancer effect used alone or in combination with conventional chemotherapeutic agents. However, the mechanisms of action for their anticancer activities are not completely understood. Herein we report that dihydroartemisinin, one of the most active derivatives of artemisinin, directly targets platelet-derived growth factor receptor-alpha (PDGFRα) to repress ovarian cancer growth and metastasis. Dihydroartemisinin directly interacts with PDGFRα and induces dephosphorylated inactivation and ubiquitin-mediated degradation of PDGFRα, which further inactivates downstream phosphoinositide 3-kinase (PI3K) and Mitogen-Activated Protein Kinase (MAPK) pathway and subsequently represses epithelial-mesenchymal transition (EMT) in terms of upregulation of epithelial marker E-cadherin and downregulation of mesenchymal markers N-cadherin and vimentin and transcriptional repressors Snail, Twist and Slug, leading to suppression of cell growth and metastasis in PDGFRα-positive ovarian cancer cells in vitro and in vivo mouse orthotopic ovarian cancer model. These findings may contribute to the development of more effective artemisinin-based targeted compounds as novel target therapy for the treatment of human cancers.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1980. doi:1538-7445.AM2012-1980