Diallyl trisulfide inhibits cell migration and invasion of human melanoma a375 cells via inhibiting integrin/facal adhesion kinase pathway.

Abstract

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.

• Authors: Hsiao-Chi Wang, Yung-Lin Chu, Shu-Chen Hsieh, Lee-Yan Sheen
• Journal: Environmental toxicology (Environ Toxicol) Vol. 32 Issue 11 Pg. 2352-2359 (Nov 2017) ISSN: 1522-7278 [Electronic] United States
• PMID: 28741790 (Publication Type: Journal Article)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Allyl Compounds
• Antineoplastic Agents
• Integrins
• Sulfides
• diallyl trisulfide
• Focal Adhesion Protein-Tyrosine Kinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Allyl Compounds (pharmacology)
• Antineoplastic Agents (pharmacology)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Focal Adhesion Protein-Tyrosine Kinases (metabolism)
• Humans
• Integrins (metabolism)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Melanoma (drug therapy)
• Phosphorylation
• Signal Transduction
• Skin Neoplasms (drug therapy)
• Stress Fibers (drug effects, ultrastructure)
• Sulfides (pharmacology)