The inhibitory effect of boric acid on hypoxia-regulated tumour-associated carbonic anhydrase IX

Yusuf Z. S., UYSAL T. K., ŞİMŞEK E., Nocentini A., Osman S. M., Supuran C. T., ...More

Journal of enzyme inhibition and medicinal chemistry, vol.37, no.1, pp.1340-1345, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 37 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1080/14756366.2022.2072837
  • Journal Name: Journal of enzyme inhibition and medicinal chemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, Directory of Open Access Journals
  • Page Numbers: pp.1340-1345
  • Keywords: Boric acid, carbonic anhydrase, enzyme inhibitor, isoform CA IX
  • Ankara Yıldırım Beyazıt University Affiliated: Yes

Abstract

Carbonic anhydrases (EC 4.2.1.1) catalyse the reversible hydration of CO2 into bicarbonate and protons. As a hypoxia-sensitive and tumour-associated isoform, isoform CA IX, is significantly overexpressed in various malignancies, being a validated target for new anticancer/antimetastatic drugs. A multitude of studies has shown that CA IX inhibition decreases cancer cell proliferation and metastasis through pHe/pHi modulation and enhancement of ferroptosis among others. Numerous studies demonstrated increased efficacy of cytotoxic drugs combined with CA inhibitors (CAIs) in various cancer types. We tested the inhibitory effect of boric acid (BA), an inorganic Lewis acid, on CA IX as well as other isoforms (CA I, II, and XII). BA acted as a millimolar in vitro CAI, decreased proliferation of two cancer cell lines, although not strong correlations between the in vitro inhibition and in vivo effects were observed. The mechanism of antiproliferative action of BA should be investigated in more detail.