The effect of oxoflavidin on breast cancer cells migration via Src-Fak-Akt suppression and the sensitization of breast cancer cells to docetaxel-mediated apoptosis

Abstract ID 90614 Poster Board 276 Background: Breast cancer is positioned at the apex among human cancers and causes nearly the top three of all cancer mortalities worldwide especially in females. Due to their aggressive phenotypes, including metastatic potential and drug resistance, novel effective anti-neoplastic agents are urgently in need. Oxoflavidin, a phenolic glycosides compound from plants of Coelogyne fuscescens Lindl. var. brunnea, could be a fine candidate for anti-cancer approaches as it has promising activities in suppressing cancer metastasis and sensitizing chemotherapeutic action. Objective: The present study aims to investigate the effect and underlying mechanisms of oxoflavidin on breast cancer cell migration and drug sensitization. Methods: Cell viability and drug sensitization were determined by MTT assay. Metastasis behaviors were analyzed using a wound-healing, and clonogenic assay. Mechanisms of oxoflavidin against metastasis including cell migration, and epithelial-to-mesenchymal transition (EMT) were evaluated by Western blot analysis and immunofluorescence. Results: Oxoflavidin dramatically suppressed EMT in breast cancer cells by the depletion of EMT markers. Regarding the mechanisms, oxoflavidin was found to suppress EMT via inhibition of the Src-Fak-Akt signaling cascade. In addition, the results indicated that oxoflavidin also inhibited cell migration, filopodia formation, and colony formation. Finally, we demonstrated that oxoflavidin enhanced the cancer cell response to docetaxel-mediated apoptosis induction. Conclusion: These findings revealed novel pharmacological actions and the underlying mechanisms of oxoflavidin in inhibited breast cancer cell migration via EMT suppression. Moreover, the downregulation of EMT markers in response to the compound inhibited cell metastasis and sensitized breast cancer cells to docetaxel-mediated apoptosis. This work was supported by Grants for development of new faculty staff, Ratchadaphiseksomphot Fund, Chulalongkorn University.