Tectorigenin functions as a potential drug for melanoma treatment via inhibition of cell growth, migration and aerobic glycolysis

Abstract

Purpose: To investigate the role of tectorigenin (TG) in melanoma cells. Methods: Viability of A375 and A2058 melanoma cells was determined by cell counting kit (CCK-8) assay. Cell cycle progression was  analyzed by 5-ethynyl-2’-deoxyuridine (EdU) staining. Migration and invasion of melanoma cells were determined by Transwell assay. The  epithelial-mesenchymal transition (EMT) of melanoma cells was investigated by determining expression of E-Cadherin and Snail. Expression of glucose transporter 1 (GLUT1) and lactose dehydrogenase A (LDHA) was assessed via western blotting. Glucose and lactate  production was evaluated by corresponding assay kit. The NOX4 and FOXM1 expressions were determined using western blotting.             Results: Tectorigenin inhibited proliferation, migration and invasion of A375 and A2058 melanoma cells. Tectorigenin regulated cell cycle  progression by decreasing the number of cells in S-phase and significantly inhibited snail expression and increased expression of  E-Cadherin (p < 0.05), thus inhibiting the EMT of A375 and A2058 cells. Tectorigenin inhibited expression of GLUT1 and LDHA, thereby leading to reduction in glucose consumption and lactate production. It also significantly inhibited expressions of NOX4 and FOXM1 (p <  0.05), indicating an inhibitory effect on the activity of NOX4/FOXM1 pathway. Conclusion: Tectorigenin inhibits aerobic glycolysis, growth  and migration in melanoma cells by suppressing the activity of NOX4/FOXM1 pathway, suggesting its potential in melanoma treatment.