Turkish Journal of Biochemistry, vol.46, no.6, pp.679-684, 2021 (SCI-Expanded)
© 2021 Beyza Ecem Öz Bedir et al., published by De Gruyter.Objectives: To determine the effects of hypoxia-inducible factors (HIF)-1 inhibitors on carbonic anhydrase-IX (CA-IX) enzyme and vascular endothelial growth factor (VEGF) in melanoma. The HIF-1 pathway induces tumor growth and metastasis by stimulating the expression of CA-IX enzyme and VEGF proteins. Methods: We evaluated the inhibition effects of Acriflavine and Echinomycin on CA-IX enzyme and VEGF in WM115 (primary) and SKMEL30 (metastatic) cell lines in normoxic and hypoxic conditions with Enzyme Linked Immunosorbent Assay. The cytotoxic activity of HIF-1 inhibitors was performed by using WST-1 assay. All experiments were performed at 450 nm using Epoch™ Microplate Spectrophotometer. Results: IC50 values were observed with a concentration of 3 μmol/L for Echinomycin and Acriflavine in the WST-1 assay. Decreased CA-IX and VEGF levels were determined in both normoxia and hypoxia after inhibitors’ treatment with WM115 and SKMEL30 cell lines (p<0.05). Inhibitory effect of HIF-1 inhibitors on CA-IX and VEGF proteins was observed in cell lines WM115 and SKMEL30. Conclusions: Due to the importance of our study, using HIF-1 inhibitors may be an alternative treatment for melanoma. Also to design new HIF-1 inhibitor derivatives is a promising approach for further studies targeting CA-IX enzyme and VEGF.