Regulation of MMP-9 protein expression level in response to treatment of iron chelator, desferrioxamine

Abstract

Metastasis is main cause of death in cancer patients. Active matrix metalloproteinases (MMPs) play a critical role in tumor invasion and metastasis. Many studies have shown that reactive oxygen species (ROS) increase the expression level and activation of MMPs through mitogen-activating protein kinase (MAPK) signaling pathway. In a cell, hydrogen peroxide, a kind of ROS, is metabolized hydroxyl radical by intracellular iron ions. Treatment of iron chelator desferrioxamine (DFO) co-treated with PMS for sustained hydrogen peroxide generation accumulates intracellular hydrogen peroxide that induces the up-regulation of MMP-9. The MMP-9 expression is activated through p38 MAPK signaling pathway. The phosphorylation of p38 MAPK is increased as the intracellular hydrogen peroxide accumulated. Phosphorylated p38 MAPK increases the translocation of NF-κB into a nucleus. Inhibition of p38 MAPK signaling pathway decreases the NF-κB translocation. And inhibition of NF-κB activation reduces the MMP-9 expression level. So, it is found that DFO-PMS co-treatment accumulates intracellular hydrogen peroxide that activate the MMP-9 expression level through p38/NF-κB pathway.