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

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 MMPp-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, EeRK, PpI-3K, NFκB and also EeGFR and downregulates pro-MMPp-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 upregulates TIMPp-1 expression.Conclusions: Our study may help to understand the role of ATRA as a regulator of MMPp-9 and the possible signaling pathways which are involved in this ATRA mediated downregulation of MMP-9. © 2010 Landes Bioscience.