The Aquaporin-3-Inhibiting Potential of Polyoxotungstates

Abstract

Polyoxometalates (POMs) are of increasing interest due to their proven anticancer activities. Aquaporins (AQPs) were found to be overexpressed in tumors bringing particular attention to their inhibitors as anticancer drugs. Herein, we report for the first time the ability of polyoxotungstates (POTs), such as of Wells–Dawson P2W18, P2W12, and P2W15, and Preyssler P5W30 structures, to affect aquaporin-3 (AQP3) activity and impair melanoma cell migration. The tested POTs were revealed to inhibit AQP3 function with different effects, with P2W18, P2W12, and P5W30 being the most potent (50% inhibitory concentration (IC50) = 0.8, 2.8, and 3.2 µM), and P2W15 being the weakest (IC50 > 100 µM). The selectivity of P2W18 toward AQP3 was confirmed in yeast cells transformed with human aquaglyceroporins. The effect of P2W12 and P2W18 on melanoma cells that highly express AQP3 revealed an impairment of cell migration between 55% and 65% after 24 h, indicating that the anticancer properties of these compounds may in part be due to the blockage of AQP3-mediated permeability. Altogether, our data revealed that P2W18 strongly affects AQP3 activity and cancer cell growth, unveiling its potential as an anticancer drug against tumors where AQP3 is highly expressed.

Polyoxometalates in solution: speciation under spotlight

“…24C) to affect aquaporin-3 (AQP3) activity and impair melanoma cell migration has been recently tested. 259 The careful speciation investigation of respective POT clusters at physiological pH 7.4 (phosphate-buffered saline medium; NaCl, 137 mmol L À1 ; KCl, 2.7 mmol L À1 ; Na 2 HPO 4 , 10 mmol L À1 ; KH 2 PO 4 , 1.8 mmol L À1 ) and in water by 31 P NMR analysis to address cluster species responsible for interaction in solution was performed. Solutions of the most promising AQP3 inhibitor, {P 2 W 18 }, contain intact Wells-Dawson anions, along with the mono-lacunary {P 2 W 17 }, while in the spectra of {P 2 W 12 } and {P 2 W 15 } only mono-lacunary species are present in PBS buffer.…”

The Ca2+-ATPase Inhibition Potential of Gold(I, III) Compounds

“…It is worth mentioning that within a physiological pH range (required for optimal activity of Ca 2+ -ATPases and in the majority of biological investigations), the gold compounds are not expected to undergo partial hydrolysis as it occurs for instance with polyoxometalates studies, where the chemical species inducing the effects should be ascertain [36]. However, in the experiments referred to above, dealing with the determination of the type of inhibition and IC 50 values, it was observed that the incubation of the gold(I) or gold(III) compounds in the medium did not affect the inhibition of the enzyme, suggesting that the compounds are stable under the experimental conditions used.…”

Vanadium and Melanoma: A Systematic Review

“…The past decades have marked important advances in the traditional view of many roles that metals and their compounds play in biological systems. In fact, metals, inorganic compounds and/or metals-organic frameworks show a diversity of properties that allowed them to present several and distinct biological, environmental and health applications [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Recent insights into metals applications includes for instance, zinc nanoparticles as feed additives showing more efficiency than zinc salts, increasing growth not only in fish [1] but also in plants [2], besides preventing metal contaminants accumulation [2] and normalizing antioxidant biomarkers [1,2].…”

“…Polyoxotungstates (POTs), such as decatungstate (W 10 O 32 4− ), have shown, by photocatalytic activity, to decompose antibiotics namely sulfasalazine and sulfapyridine with different specificities and rates [5]. Besides green biotechnology applications, it was suggested that some POTs hamper melanoma cancer cells growth through inhibition of aquaporin-3 activity [6], whereas others POTs as well as gold compounds showed specific inhibitory activities for P-type ATPases [7,8].…”