HIF-1 inhibitors: differential effects of Acriflavine and Echinomycin on tumor associated CA-IX enzyme and VEGF in melanoma

Autor: Ender Şimşek, Elif Ercan, Tuğba Kevser Uysal, İbrahim Karakuş, Emine Terzi, Beyza Ecem Öz Bedir, Ozen Ozensoy Guler
Rok vydání: 2021
Předmět:
Zdroj: Turkish Journal of Biochemistry. 46:679-684
ISSN: 1303-829X
Popis: 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 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.
Databáze: OpenAIRE