Abstract
The vitamin A derivative all-trans retinoic acid (ATRA) is considered as a potent chemotherapeutic drug for its capability of regulating cell growth and differentiation. We aimed to study the effect of ATRA on MMP-9 in MDA-MB-231, human breast cancer cells and the probable molecular mechanisms through which ATRA exerts its effect.
Results:
Our experimental findings demonstrate that ATRA enters into the nucleus and regulates various signaling pathways viz. Integrin, FAK, ERK, PI-3K, NF-κB and also EGFR and down regulates pro-MMP-9 activity as well as its expression. As a result MDA-MB-231 cell migration on fibronectin medium gets retarded in presence of ATRA. ATRA up regulates TIMP-1 expression. Our study may help to understand the role of ATRA as a regulator of MMP-9 and the possible signaling pathways which are involved in this ATRA mediated down regulation of MMP-9.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Cadherins / metabolism
-
Cell Line, Tumor
-
Cell Movement / drug effects
-
Cell Survival / drug effects
-
Culture Media / pharmacology
-
Down-Regulation / drug effects*
-
Epidermal Growth Factor / pharmacology
-
ErbB Receptors / metabolism
-
Fibronectins / pharmacology
-
Focal Adhesion Protein-Tyrosine Kinases / metabolism
-
Gene Expression Regulation, Neoplastic / drug effects
-
Humans
-
Integrins / metabolism
-
Ligands
-
Matrix Metalloproteinase 9 / genetics
-
Matrix Metalloproteinase 9 / metabolism*
-
NF-kappa B / metabolism
-
Receptors, Retinoic Acid / metabolism
-
Signal Transduction / drug effects*
-
Tissue Inhibitor of Metalloproteinase-1 / metabolism
-
Tretinoin / pharmacology*
-
Up-Regulation / drug effects
-
Vascular Endothelial Growth Factor A / metabolism
Substances
-
Cadherins
-
Culture Media
-
Fibronectins
-
Integrins
-
Ligands
-
NF-kappa B
-
Receptors, Retinoic Acid
-
Tissue Inhibitor of Metalloproteinase-1
-
Vascular Endothelial Growth Factor A
-
retinoic acid binding protein I, cellular
-
Tretinoin
-
Epidermal Growth Factor
-
ErbB Receptors
-
Focal Adhesion Protein-Tyrosine Kinases
-
Matrix Metalloproteinase 9