title: Inhibition of integrins αv/α5-dependent functions in melanoma cells by an ECD-disintegrin acurhagin-C.
abstract: Acurhagin-C, a Glu-Cys-Asp (ECD)-disintegrin from Agkistrodon acutus venom, has been reported as an endothelial apoptosis inducer, previously. Here we further evaluate its potential applications in cancer therapy. In vitro assays indicated that acurhagin-C not only may influence the cell viability at higher concentration, but also can potently and dose-dependently decrease cell proliferation in murine B16-F10 melanoma. Otherwise, it also had a dose-dependent inhibition on B16-F10 cell adhesion to extracellular matrices, collagen VI, gelatin B and fibronectin, as well as disturbed transendothelial migration of B16-F10 cell. Morphological study found that acurhagin-C dramatically affected B16-F10 cell adhesion to immobilized fibronectin, leading to the formation of multicellular aggregates with rounded shape. Detected by flow cytometry, acurhagin-C was able to induce B16-F10 cell apoptosis and alter cell cycle distribution through its interactions with integrins αv/α5, and thereafter initiation the apoptotic pathways of caspase-8/-9. Furthermore, acurhagin-C could synergistically enhance the anti-proliferative activity of methotrexate in B16-F10 cells and human melanoma SK-MEL-1 cells, without diminishing the growth of human epidermal melanocytes. Taken together, acurhagin-C proved to be a potent inhibitor of integrin-based functions in melanoma cells by activating the complex apoptotic pathways.
authors: Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan.
authors: Chun-Ho
authors: CH
authors: Shih
authors: Tin-Bin
authors: TB
authors: Chiang
authors: Wen-Jeng
authors: WJ
authors: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002448:Cell Adhesion; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019483:Disintegrins / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D039482:Integrin alpha5 / Q000378:metabolism*; D039564:Integrin alphaV / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects / Q000502:physiology; D008546:Melanoma, Experimental; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D019483:Disintegrins; D039482:Integrin alpha5; D039564:Integrin alphaV; D010446:Peptide Fragments; C552884:acurhagin-C protein, Agkistrodon acutus