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.

Is carbonic anhydrase inhibition useful as a complementary therapy of Covid-19 infection?

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.

Do CO2 and oxidative stress induce cancer?: a brief study about the evaluation of PON 1, CAT, CA and XO enzyme levels on head and neck cancer patients.

Head and neck cancer (HNC) is one of the most common malignancies in the world. HNC is a group of cancers that starts in the mouth, nose, throat, larynx, sinuses, or salivary glands. According to this section of the body parts; induction of cancer can be associated with CO2 and oxidative stress. The aim of this study is to assess the activities of carbonic anhydrase (CA), catalase (CAT), paraoxonase1 (PON1), and xanthine oxidase (XO) activities in 89 HNC patients and 115 healthy volunteers. Paraoxonase1 activity was found lower in HNC cancer patients. There is no statistically significant difference between patients and controls for catalase, carbonic anhydrase, and xanthine oxidase enzyme levels. According to this results, paraoxonase1 levels could be a candidate as an oxidative marker in HNC patients, but further studies are needed to investigate the other type of cancer related PON1 and the other enzyme levels.