title: 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.
authors.affiliation: Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.forename: Chiao-Lun
authors.initials: CL
authors.lastname: Chu
authors.forename: Yaw-Syan
authors.initials: YS
authors.lastname: Fu
authors.forename: Chih-Hua
authors.initials: CH
authors.lastname: Tseng
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
authors.forename: Long-Sen
authors.initials: LS
authors.lastname: Chang
authors.forename: Shinne-Ren
authors.initials: SR
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009285:Naphthoquinones / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction / Q000187:drug effects*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; C073873:naphtho(1,2-b)furan-4,5-dione; D019061:src-Family Kinases