New Nitric Oxide-Releasing Compounds as Promising Anti-Bladder Cancer Drugs

Varela, María - López, Miriam - Ingold, Mariana - Alem, Diego - Perini, Valentina - Perelmuter, Karen - Bollati-Fogolín, Mariela - López, Gloria V. - Hernandez, Paola

Resumen:

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 1 and 3 exerted a high antiproliferative activity against bladder cancer cells through DNA damage and survivin downregulation. In addition, compound 3 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.


Detalles Bibliográficos
2023
Agencia Nacional de Investigación e Innovación
Comisión Sectorial de Investigación Científica
NF-κB
Bladder cancer
Furoxans
Nitric oxide donors
Survivin
Ciencias Médicas y de la Salud
Biotecnología de la Salud
Tecnologías que involucran la manipulación de células, tejidos, órganos o todo el org
Inglés
Institut Pasteur de Montevideo
IPMON en REDI
https://hdl.handle.net/20.500.12381/3243
https://doi.org/10.3390/biomedicines11010199
Acceso abierto
Reconocimiento 4.0 Internacional. (CC BY)
Resumen:
Sumario: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 1 and 3 exerted a high antiproliferative activity against bladder cancer cells through DNA damage and survivin downregulation. In addition, compound 3 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.