The inhibitory effect of boric acid on hypoxia-regulated tumour-associated carbonic anhydrase IX
Carbonic anhydrases (EC 220.127.116.11) 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.
Boric acid at a concentration of 2.8 millimolar inhibits carbonic anhydrase 9 (CAIX) enzyme.
Boric acid Molar mass: 61.83 g/mol
∴ 1 mol of Boric acid = 61.83 g
1 mol = 1,000 mmol
∴ 1 mmol of Boric acid = 0.06183 g
∴ 2.8 mmol of Boric acid = 0.173124 g
So, we need 0.173124 g of Boric acid per L of blood.
There are around 5 liters of blood in the average human adult body.
5 x 0.173124 = 0.86562 g
We know that 1 g = 1000 mg and need to have 0.86562 g of Boric acid.
0.86562 x 1000 = 865.62 mg
So, 2.8 millimolar of Boric acid is equivalent to 866 milligram of Boric acid.
I do not specialize in biochemistry, these calculations may not be correct!
Carbonic anhydrase 9 (CAIX) this is an enzyme that helps extracellular CO2 to become HCO3 (bicarbonate ion). This bicarbonate ion than goes into the cell via the bicarbonate transporter and combines (via CAII enzyme) with a proton resulting CO2 and H20 which are finally pushed out through the cell membrane. This is a way for the cancer cell to annihilate intracellular protons and thus mantain an increased intracellular pH – well known to be over expressed in many cancers