Diallyl trisulfide inhibits cell migration and invasion of human melanoma a375 cells via inhibiting integrin/facal adhesion kinase pathway.
Melanoma is the leading cause of death from skin disease due to its propensity for metastasis. Studies have shown that integrin-mediated focal adhesion kinase (FAK) signal pathway is implicated in cell proliferation, survival and metastasis of tumor cells. Our previous results indicated that diallyl trisulfide (DATS) provided its antimelanoma activity via inducing cell cycle arrest and apoptosis. The aim of this study was to explore DATS mediated antimetastatic effect and the corresponding mechanism in human melanoma A375 cells. We found that DATS exhibited an inhibitory effect on the abilities of migration and invasion in A375 cells under noncytotoxic concentrations analyzed by wound healing assays and Matrigel invasion chamber system. DATS attenuated invasion of A375 cells with characteristic of decreased activities and protein expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9. Moreover, DATS exerted an inhibitory effect on cell adhesion of A375 cells, which is in correlation with the change in integrin signaling pathway. Results of Western blotting showed that DATS decreased the levels of several integrin subunits, including α4, α5, αv, β1, β3 and β4. Subsequently, DATS induced a strong decrease in total FAK, phosphorylated FAK Tyr-397,-576, -577, and disorganized F-actin stress fibers, resulting in a nonmigratory phenotype. These results suggest that the antimetastatic potential of DATS for human melanoma cells might be due to the disruption of integrin/FAK signaling pathway.
['Wang|Hsiao-Chi|HC|', 'Chu|Yung-Lin|YL|', 'Hsieh|Shu-Chen|SC|', 'Sheen|Lee-Yan|LY|']
D000498:Allyl Compounds D000970:Antineoplastic Agents D002448:Cell Adhesion D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D051416:Focal Adhesion Protein-Tyrosine Kinases D006801:Humans D016023:Integrins D020778:Matrix Metalloproteinase 2 D020780:Matrix Metalloproteinase 9 D008545:Melanoma D010766:Phosphorylation D015398:Signal Transduction D012878:Skin Neoplasms D022502:Stress Fibers D013440:Sulfides
migration invasion metastasis DATS skin cancer cells