Retinoic acid (RA), a metabolite of vitamin A, is known to be a chemotherapeutic agent. The anti-carcinogenic effects of retinoids are in part due to their ability to inhibit proliferation of cancer cells, including tumors of lung, breast and leukemia. Matrix metalloproteinases (MMPs) are key enzymes in the degradation of extracellular matrix, and their expressions may be regulated in cancer metastasis. In this study, we investigated the effects and mechanisms of RA on activity and expression of MMPs in HT1080 cells. We found that RA inhibited the cell proliferation in a dose-dependent manner by phase contrast microscope and MTT assay in HT1080. And also, RA dramatically increased the expression and activity of MMP-9 and MMP-2 in dose- and time- dependent manner as determined by gelatin zymography assay and Western blot analysis. Phosphorylation of p38 kinase and C-Jun N-terminal Kinase (JNK) was inhibited by RA in HT1080 cells. Inhibition of p38 kinase and JNK with SB203580 and SP600125, respectively, potentiated RA-induced MMP-9/-2 activity and expression in HT1080 cells. Our results suggest that RA regulates activity and expression of MMP-9/-2 through p38 kinase and JNK pathway in HT1080 fibrosarcoma cells. (Cancer Prev Res 17, 0-211, 2012)

Keywords: Retinoic acid, MMP-9, MMP-2, p38 kinase, JNK, HT1080