All-trans retinoic acid (ATRA) downregulates MMP-9 by modulating its regulatory molecules

Cell Adh Migr. 2010 Jul-Sep;4(3):409-18.
Dutta A, Sen T, Chatterjee A.
Cell Adh Migr. 2010 Jul-Sep;4(3):409-18.
Acido all-trans retinoico (ATRA) è considerato un potente farmaco chemioterapico per la sua capacità di regolazione della crescita cellulare in coltura anche su cellule tumorali umane del seno (MMP-9/MDA-MB-231).
ATRA/carcinoma mammario.

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.