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

Abstract

Abstract. 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 antiprolif erative effect of G-1, a marked increase in apoptotic activity was observed when cells were treated with 2x10-5 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.

Synthesis of 2-Substituted Benzothiazole Derivatives and Their In Vitro Anticancer Effects and Antioxidant Activities Against Pancreatic Cancer Cells

“…Compounds 4a and 4b were synthesized from reaction between 2-amino-thiophenol with chalcones 3a and 3b in ethanol at reflux (10 h) in good yield (Table I). All spectral data of compounds 4a and 4b ( 1 H NMR, 13 C NMR, IR, elemental analysis) corresponded with the proposed structures.…”

“…PANC-1 cells were obtained from the American Tissue Culture Collection (Manassas, VA, USA). Cells were cultured as described previously (13). In brief, cells were cultured in high glucose Dulbecco's modified Eagles medium (DMEM) (Gibco Life Technologies, Carlsbad, CA, USA) supplemented with 100 U/ml penicillin (Sigma-Aldrich, St. Louis, MO, USA) and 10% fetal bovine serum (FBS; Gibco Life Technologies) at 37˚C in a humidified atmosphere of 5% CO 2 .…”

Tamoxifen induces toxicity, causes autophagy, and partially reverses dexamethasone resistance in Jurkat T cells

“…Remarkably, GPER mediates the proliferative effect of estrogen in numerous cancer types . Accordingly, GPER agonist G‐1 was shown to inhibit tumor growth in triple‐negative breast cancer cells, adrenocortical carcinoma, lung cancer, and ovarian cancer…”

“…effect of estrogen in numerous cancer types. 9,10 Accordingly, GPER agonist G-1 was shown to inhibit tumor growth in triple-negative breast cancer cells, 11 adrenocortical carcinoma, 12 lung cancer, 13 and ovarian cancer. 14 TAM is considered as an ER antagonist and GPER agonist, 15,16 which has been the first-line targeted therapy for the management of ER positive breast cancers for almost 60 years.…”

G-1 Inhibits Breast Cancer Cell Growth via Targeting Colchicine-Binding Site of Tubulin to Interfere with Microtubule Assembly

“…However, accumulating evidence indicated that G-1 is a potent tumor growth inhibitor. Recent studies demonstrated that G-1 suppresses proliferation and induces apoptosis in numerous types of cancer cells, including: ovarian cancer (9–11), adrenocortical carcinoma (12), Lung cancer (13), cervical cancer (14), and prostate cancer (15). …”