Effect of caveolin-1 on hydrogen peroxide-mediated oxidative stress and cell death in lung carcinoma cells

Abstract

Oxidative stress plays an important role in cancer cell behavior and tumor progression. In lung cancer, various kinds of reactive oxygen species (ROS) especially hydrogen peroxide (H₂O₂) has been up-regulated in tumor microenvironment. Moreover, caveolin-1 (Cav-1) has been shown to overexpress in both primary and metastatic cancers and may be critical in the regulation of oxidative status of cancer cells. This study has reported for the first time that Cav-1 suppressed cellular oxidative stress induced by H₂O₂. The treatment of H₂O₂ in human lung carcinoma H460 cells significantly increased ROS inside the cells and resulted in cell apoptosis. Furthermore, using of specific ROS detecting assay and pretreatment with specific antioxidants revealed that superoxide anion was not associated with H₂O₂-induced oxidative stress whereas the hydroxyl radical was the key ROS which was responsible for oxidative damage in H460 cells. To study the effect of Cav-1 on H₂O₂-induced oxidative stress and cell death, H460 cells were transfected with Cav-1 overexpressing (H460/Cav-1) or knockdown plasmids (H460/shCav-1). The resulted showed that ROS level and cell death of H460/Cav-1 cells were decreased after H₂O₂ treatment in comparison to those of H460 control cells while H460/shCav-1 cells exhibited enhanced ROS signal and increased number of apoptotic cells. In conclusion, this study suggested that hydroxyl radical was the main ROS causing oxidative stress and cell death and Cav-1 protein attenuated cellular oxidative damage induced by H₂O₂ in lung carcinoma cells. These findings may provide the novel information of Cav-1 in cancer research and the better understanding on cancer resistance to ROS-generating chemotherapy.