Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
Int J Mol Sci. 2020 Apr 2;21(7):2467. doi: 10.3390/ijms21072467.
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 PW, PW, and PW, and Preyssler PW 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 PW, PW, and PW being the most potent (50% inhibitory concentration (IC) = 0.8, 2.8, and 3.2 µM), and PW being the weakest (IC50 > 100 µM). The selectivity of PW toward AQP3 was confirmed in yeast cells transformed with human aquaglyceroporins. The effect of PW and PW 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 PW strongly affects AQP3 activity and cancer cell growth, unveiling its potential as an anticancer drug against tumors where AQP3 is highly expressed.
多金属氧酸盐（POMs）由于其已被证实的抗癌活性而受到越来越多的关注。水通道蛋白（AQPs）在肿瘤中被发现过度表达，这使得它们的抑制剂作为抗癌药物引起了特别关注。在此，我们首次报道了多钨酸盐（POTs），如 Wells-Dawson PW、PW 和 PW 以及 Preyssler PW 结构，能够影响水通道蛋白-3（AQP3）活性并损害黑色素瘤细胞迁移。测试的 POTs 被证明以不同的方式抑制 AQP3 功能，其中 PW、PW 和 PW 最为有效（50%抑制浓度（IC）= 0.8、2.8 和 3.2 µM），而 PW 则最弱（IC50>100 µM）。PW 对酵母细胞中表达的人水通道蛋白的选择性在转化的酵母细胞中得到了证实。PW 和 PW 对高度表达 AQP3 的黑色素瘤细胞的影响表明，在 24 小时后细胞迁移受到了 55%至 65%的抑制，这表明这些化合物的抗癌特性可能部分归因于阻断 AQP3 介导的通透性。总的来说，我们的数据表明 PW 强烈影响 AQP3 的活性和癌细胞的生长，揭示了其作为针对高表达 AQP3 的肿瘤的抗癌药物的潜力。
