INVESTIGADORES
CADAVID VARGAS Juan Fernando
artículos
Título:
Enhanced antitumor effect of l-buthionine sulfoximine or ionizing radiation by copper complexes with 2,2´-biquinoline and sulfonamides on A549 2D and 3D lung cancer cell models
Autor/es:
CADAVID VARGAS, J. F.; VILLA PEREZ, C.; SORIA, D. B.; GUERCI, A.; DI VIRGILIO, A. L.
Revista:
JBIC Journal of Biological Inorganic Chemistry
Editorial:
Springer
Referencias:
Año: 2022
Resumen:
AbstractTwo ternary copper(II) complexes with 2,2′-biquinoline (BQ) and with sulfonamides: sulfamethazine (SMT) or sulfaquinoxaline (SDQ) whose formulae are Cu(SMT)(BQ)Cl and Cu(SDQ)(BQ)Cl·CH3OH, in what follows SMTCu and SDQCu,respectively, induced oxidative stress by increasing ROS level from 1.0 μM and the reduction potential of the couple GSSG/GSH2. The co-treatment with l-buthionine sulfoximine (BSO), which inhibits the production of GSH, enhanced the efectof copper complexes on tumor cell viability and on oxidative damage. Both complexes generated DNA strand breaks givenby?at least partially?the oxidation of pyrimidine bases, which caused the arrest of the cell cycle in the G2/M phase. Thesephenomena triggered processes of apoptosis proven by activation of caspase 3 and externalization of phosphatidylserine andloss of cell integrity from 1.0 μM. The combination with BSO induced a marked increase in the apoptotic population. Onthe other hand, an improved cell proliferation efect was observed when combining SDQCu with a radiation dose of 2 Gyfrom 1.0 μM or with 6 Gy from 1.5 μM. Finally, studies in multicellular spheroids demonstrated that even though copper(II)complexes did not inhibit cell invasion in collagen gels up to 48 h of treatment at the higher concentrations, multicellularresistance outperformed several drugs currently used in cancer treatment. Overall, our results reveal an antitumor efect ofboth complexes in monolayer and multicellular spheroids and an improvement with the addition of BSO. However, onlySDQCu was the best adjuvant of ionizing radiation treatment.