G-1

G-1 is a nonsteroidal, high-affinity and selective agonist of GPR30 with a Ki of 11 nM.

Signaling Pathways >> Others >> Estrogen Receptor/ERR

Research Areas >> Cancer

Ki: 11 nM (GPR30)[1]

G-1 is a nonsteroidal, high-affinity and selective agonist of GPR30 with a Ki of 11 nM[1]. Treatment with G-1 (10 μM and 100 μM) for 48 and 72 h significantly decreases cell proliferation (P<0.001). At 72 h, the IC50 value for G-1 is calculated to be 20 μM. Treatment of A549 cells with G-1 at a concentration of 20 μM reveals a significant increase in apoptosis, consistent with its antiproliferative effect (P<0.001)[2]. Cell cycle analysis of H295R cells after 24 h of G-1 treatment demonstrates a cell cycle arrest in the G2 phase. The presence of G-1 increases Bax expression while decreases Bcl-2[3].

The results at 14 days post-injury show that the Basso mouse scale (BMS) scores are significantly higher in the G-1 group compared with the other groups (P<0.05). The number of caspase-3-positive cells in the cross sections is counted, and G-1 group has fewer positive cells compare with the other groups (P<0.05), and there is no difference between the two groups (P>0.05)[1]. G-1 administration produces a statistically significant decrease in tumor volume from day 14 post treatment. Grafted tumors harvested after three-week treatment with G-1 show a significant decrease in tumor weight compare to vehicle treated animals[3].

A549 human lung cancer cells are treated with various concentrations (10 nM, 100 nM, 1 μM, 10 μM and 100 μM) of G-1 in 96-well plates and incubated for 48 or 72 h. Following incubation, MTT solution is added to each well at a concentration of 0.5 mg/mL, and incubated for 4 h at 37°C. At the end of this period, 100 µL DMSO solvent is added to each well. The absorbance values [optical density (OD)] at 570 nm of the solution in each well are read using a spectrophotometer[2].

Four-week-old nu/nu-Forkhead box N1nu female mice are used in this study. H295R cells, 6×106, suspended in 100 μL PBS, are combined with 30 μL of Matrigel (4 mg/mL) and injected subcutaneously in the shoulder of each animal. Mice are treated 21 days after cell injection, when tumors have reached an average volume of about 200 mm3. Animals are randomly assigned to be treated with vehicle or G-1 at a concentration of 2 mg/kg/daily. Drug tolerability is assessed in tumor-bearing mice in terms of: a) lethal toxicity, i.e. any death in treated mice occurring before any death in control mice; b) body weight loss percentage=100-[(body weight on day x/body weight on day 1)×100], where x represents a day during the treatment period. Animals are sacrificed by cervical dislocation 42 days after cell injection[3].

[1]. Cheng Q, et al. G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice. Biosci Rep. 2016 Aug 31;36(4). pii: e00373.

[2]. Kurt AH, et al. Oxidative/antioxidative enzyme-mediated antiproliferative and proapoptotic effects of the GPER1 agonist G-1 on lung cancer cells. Oncol Lett. 2015 Nov;10(5):3177-3182.

[3]. Chimento A, et al. GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growth in vitro and in vivo. Oncotarget. 2015 Aug 7;6(22):19190-203.

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