HIF-1 inhibitors: differential effects of Acriflavine and Echinomycin on tumor associated CA-IX enzyme and VEGF in melanoma Melanomda HIF-1 inhibitörleri olan Akriflavin ve Ekinomisin’in tümör ilişkili CA-IX enzimi ve VEGF proteini üzerine inhibisyon etkilerinin incelenmesi


Bedir B. E. Ö., TERZİ E., ŞİMŞEK E., Karakuş İ., UYSAL T. K., ERCAN E., ...More

Turkish Journal of Biochemistry, vol.46, no.6, pp.679-684, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 46 Issue: 6
  • Publication Date: 2021
  • Doi Number: 10.1515/tjb-2021-0085
  • Journal Name: Turkish Journal of Biochemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE, Food Science & Technology Abstracts, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.679-684
  • Keywords: Acriflavine, CA-IX, Echinomycin, hypoxia, melanoma, VEGF, Akriflavin, CA-IX, Ekinomisin, Hipoksi, Melanom, VEGF
  • Ankara Yıldırım Beyazıt University Affiliated: Yes

Abstract

© 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.