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Naphtho[1,2-b]furan-4,5-dione inhibits MDA-MB-231 cell migration and invasion by suppressing Src-mediated signaling pathways.

Abstract
Naphtho[1,2-b]furan-4,5-dione (NFD), a bioactive component of Avicennia marina, has been demonstrated to display anti-cancer activity. Breast cancer is a highly malignant carcinoma and most deaths of breast cancer are caused by metastasis. In this study, we showed that NFD blocked migration and invasion of MDA-MB-231 breast cancer cells without affecting apoptosis or growth arrest. NFD caused significant block of Src kinase activity in MDA-MB-231 cells. Moreover, NFD treatment was correlated with reduced phosphorylation of FAK at Tyr 576/577, 861 and 925 sites, p130(Cas) at Tyr 410, and paxillin at Tyr 118. NFD also suppressed the activation of phosphatidylinositol 3-kinase/Akt. Consistent with inhibition of these signaling pathways and invasion, NFD reduced the expression of matrix metalloproteinase-9. Furthermore, Src antagonist PP2 caused a significant decrease in the phosphorylation of FAK, p130(Cas), paxillin, and PI3K/Akt. Our findings provide evidences that NFD inhibits Src-mediated signaling pathways involved in controlling breast cancer migration and invasion, suggesting that it has a therapeutic potential in breast cancer treatment.
AuthorsPei-Chien Tsai, Chiao-Lun Chu, Yaw-Syan Fu, Chih-Hua Tseng, Yeh-Long Chen, Long-Sen Chang, Shinne-Ren Lin
JournalMolecular and cellular biochemistry (Mol Cell Biochem) Vol. 387 Issue 1-2 Pg. 101-11 (Feb 2014) ISSN: 1573-4919 [Electronic] Netherlands
PMID24162594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Naphthoquinones
  • naphtho(1,2-b)furan-4,5-dione
  • src-Family Kinases
Topics
  • Antineoplastic Agents (pharmacology)
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement (drug effects)
  • Drug Screening Assays, Antitumor
  • Humans
  • Naphthoquinones (pharmacology)
  • Neoplasm Invasiveness
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Signal Transduction (drug effects)
  • src-Family Kinases (antagonists & inhibitors, metabolism)

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