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

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.

Automated summary

Carbonic anhydrases (CAs) are enzymes that catalyze the reversible hydration of CO2. One isoform, CA IX, is significantly overexpressed in various malignancies and is considered a validated target for new anticancer drugs. Inhibition of CA IX has been shown to decrease cancer cell proliferation and metastasis. Boric acid (BA) was tested as a CA IX inhibitor and was found to decrease proliferation of cancer cells in vitro, although the correlation between in vitro inhibition and in vivo effects was not strong. The mechanism of action of BA as an antiproliferative agent needs further investigation.