Varela María, López Miriam, Ingold Mariana, Alem Diego, Perini Valentina, Perelmuter Karen, Bollati-Fogolín Mariela, López Gloria V, Hernández Paola
Departamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, Montevideo 11600, Uruguay.
Laboratorio de Biología Vascular y Desarrollo de Fármacos, Institut Pasteur Montevideo, Mataojo 2020, Montevideo 11400, Uruguay.
Biomedicines. 2023 Jan 12;11(1):199. doi: 10.3390/biomedicines11010199.
Bladder cancer is a worldwide problem and improved therapies are urgently needed. In the search for newer strong antitumor compounds, herein, we present the study of three nitric oxide-releasing compounds and evaluate them as possible therapies for this malignancy. Bladder cancer cell lines T24 and 253J were used to evaluate the antiproliferative, antimigratory, and genotoxic effects of compounds. Moreover, we determined the NF-κB pathway inhibition, and finally, the survivin downregulation exerted by our molecules. The results revealed that compounds and exerted a high antiproliferative activity against bladder cancer cells through DNA damage and survivin downregulation. In addition, compound reduced bladder cancer cell migration. We found that nitric oxide donors are promising molecules for the development of a new therapeutic targeting the underlying mechanisms of tumorigenesis and progression of bladder cancer.
膀胱癌是一个全球性问题，迫切需要改进治疗方法。在寻找更新的强效抗肿瘤化合物的过程中，我们在此展示了对三种一氧化氮释放化合物的研究，并评估它们作为这种恶性肿瘤可能的治疗方法。使用膀胱癌细胞系T24和253J来评估化合物的抗增殖、抗迁移和遗传毒性作用。此外，我们确定了分子对NF-κB途径的抑制作用，以及最终对生存素的下调作用。结果显示，化合物 和 通过DNA损伤和生存素下调对膀胱癌细胞具有高抗增殖活性。此外，化合物 减少了膀胱癌细胞的迁移。我们发现一氧化氮供体是开发针对膀胱癌发生和进展潜在机制的新疗法的有前景的分子。
