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.

The inhibitory effect of boric acid on hypoxia-regulated tumour-associated carbonic anhydrase IX / Yusuf, Zainab Saad; Uysal, Tugba Kevser; Simsek, Ender; Nocentini, Alessio; Osman, Sameh Mohamed; Supuran, Claudiu T; Özensoy Güler, Özen. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6374. - ELETTRONICO. - 37:(2022), pp. 1340-1345. [10.1080/14756366.2022.2072837]

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

Nocentini, Alessio;Supuran, Claudiu T;
2022

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.
37
1340
1345
Yusuf, Zainab Saad; Uysal, Tugba Kevser; Simsek, Ender; Nocentini, Alessio; Osman, Sameh Mohamed; Supuran, Claudiu T; Özensoy Güler, Özen
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1289745
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact