title: Combined effects of furanodiene and doxorubicin on the migration and invasion of MDA-MB-231 breast cancer cells in vitro.
abstract: Furanodiene is one of the major bioactive components isolated from the natural product of the plant, Curcuma wenyujin Y.H. Chen et C. Ling. Furanodiene has been found to exert anticancer effects in various types of cancer cell lines, as well as exhibit antimetastatic activities. However, the antimetastatic capacity of furanodiene in combination with the common chemotherapy drug doxorubicin has not been investigated. We found that doxorubicin at a non-toxic concentration induced cell migration and cell invasion in highly metastatic breast cancer cells. Combinational treatments with furanodiene and doxorubicin blocked the invasion and migration of MDA-MB-231 breast cancer cells in vitro. We also clarified the effects of the combination on the signaling pathways involved in migration, invasion, and cytoskeletal organization. When combined with doxorubicin, furanodiene downregulated the expression of integrin αV and β-catenin and inhibited the phosphorylation of paxillin, Src, focal adhesion kinase (FAK), p85, and Akt. Moreover, combinational treatments also resulted in a decrease in matrix metalloproteinase-9 (MMP-9). Further study demonstrated that the co-treatments with furanodiene did not significantly alter the effects of doxorubicin on the tubulin cytoskeleton, represented by no influence on the expression levels of RhoA, Cdc42, N-WASP, and α/β tubulin. These observations indicate that furanodiene is a potential agent that may be utilized to improve the anticancer efficacy of doxorubicin and overcome the risk of chemotherapy in highly metastatic breast cancer.
authors.affiliation: Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR 999078, P.R. China.
authors.forename: Zhang-Feng
authors.initials: ZF
authors.lastname: Zhong
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tian
authors.affiliation: Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR 999078, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.affiliation: Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, IL 60611, USA.
authors.forename: Wen-An
authors.initials: WA
authors.lastname: Qiang
authors.affiliation: Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR 999078, P.R. China.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Wang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D030024:Curcuma / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000096:biosynthesis; D005663:Furans / Q000008:administration & dosage* / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006574:Heterocyclic Compounds, 2-Ring / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010936:Plant Extracts / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005663:Furans; D006574:Heterocyclic Compounds, 2-Ring; D009363:Neoplasm Proteins; D010936:Plant Extracts; C442489:furanodiene; D004317:Doxorubicin; D051417:Focal Adhesion Kinase 1; D020780:Matrix Metalloproteinase 9