Oxidative/antioxidative enzyme-mediated antiproliferative and proapoptotic effects of the GPER1 agonist G-1 on lung cancer cells.

Estrogen mediates fast signal responses or transcriptional events via G protein-coupled estrogen receptor 1 (GPER1). However, there is no data on the effect of GPER1 on lung cancer cell proliferation and apoptosis. The present study aimed to analyze the anticancer effects of the GPER1 agonist G-1 on A549 human lung cancer cells. A549 cells were treated with 17β-estradiol and G-1, and cell proliferation was analyzed using MTT and WST assays. In addition, the apoptotic effects induced by G-1 were investigated using acridine orange/ethidium bromide staining. A549 cells were treated with a half maximal inhibitory concentration of G-1 for 72 h, and nitric oxide (NO) levels and superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) enzyme activities were analyzed by spectrophotometry. The results revealed that G-1 significantly decreased cell proliferation. In addition to the antiproliferative effect of G-1, a marked increase in apoptotic activity was observed when cells were treated with 2×10-5 M G-1. Furthermore, G-1 increased NO levels, and SOD and GPx activity. These findings indicate that the GPER1 agonist G-1 is able to exert antiproliferative and proapoptotic effects on A549 cells, and that oxidant and antioxidant molecules may mediate these effects.