Depletion of CD147 sensitizes human malignant melanoma cells to hydrogen peroxide-induced oxidative stress

Background: Increased sensitivity to reactive oxygen species (ROS) contributes to the effectiveness of therapeutic strategies in patients with malignant melanoma (MM). CD147, a cell surface receptor for cyclophilin A (CypA), is thought to exert antioxidant activities. Objective: To understand the influences and mechanisms of CD147 on proliferation, apoptosis and redox state of A375 cells under H2O2-induced oxidative stress. Methods: The effect of CD147 silencing on cell viability, apoptosis, the generation of ROS, superoxide dismutase (SOD) activity, and the malondialdehyde (MDA) level that reflects oxidative damage, was measured in human malignant melanoma cell line A375 treated or untreated with hydrogen peroxide (H2O2). Results: In A375 cells, CD147 silencing increased the H2O2-induced inhibition of cell viability, H2O2-induced apoptosis, H2O2-mediated ROS- and MDA generation, and the H2O2-triggered decrease in SOD activity. Conclusions: Our results demonstrated that CD147 silencing increased cellular ROS and destroyed the intrinsic antioxidant defenses in A375, indicating that CD147 exerts a cytoprotective effect against H2O2-induced oxidative damage. (C) 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.