Sulfonamide-derived Dithiocarbamate Gold(i) complexes induce the apoptosis of colon cancer cells by the activation of Caspase 3 and redox imbalance

Quero, Javier (Universidad de Zaragoza) ; Royo, José Carlos ; Fodor, Beatrice ; Gimeno, María Concepción ; Osada, Jesús (Universidad de Zaragoza) ; Rodríguez Yoldi, María Jesús (Universidad de Zaragoza) ; Cerrada, Elena (Universidad de Zaragoza)

Resumen: Two new families of dithiocarbamate gold(I) complexes derived from benzenesulfonamide with phosphine or carbene as ancillary ligands have been synthesized and characterized. In the screening of their in vitro activity on human colon carcinoma cells (Caco-2), we found that the more lipophilic complexes—those with the phosphine PPh3—exhibited the highest anticancer activity whilst also displaying significant cancer cell selectivity. Au(S2CNHSO2C6H5)(PPh3)] (1) and Au(S2CNHSO2-p-Me-C6H4)(IMePropargyl)] (8) produce cell death, probably by intrinsic apoptosis (mitochondrial membrane potential modification) and caspase 3 activation, causing cell cycle arrest in the G1 phase with p53 activation. Besides this, both complexes might act as multi-target anticancer drugs, as they inhibit the activity of the enzymes thioredoxin reductase (TrxR) and carbonic anhydrase (CA IX) with the alteration of the redox balance, and show a pro-oxidant effect.

Idioma: Inglés

DOI: 10.3390/biomedicines10061437

Año: 2022

Publicado en: Biomedicines 10, 6 (2022), 1437 [19 pp.]
ISSN: 2227-9059

Factor impacto JCR: 4.7 (2022)

Categ. JCR: PHARMACOLOGY & PHARMACY rank: 68 / 278 = 0.245 (2022) - Q1 - T1
Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 92 / 285 = 0.323 (2022) - Q2 - T1
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 54 / 136 = 0.397 (2022) - Q2 - T2

Factor impacto CITESCORE: 3.7 - Medicine (Q2) - Biochemistry, Genetics and Molecular Biology (Q3)

Factor impacto SCIMAGO: 0.897 - Medicine (miscellaneous) (Q1) - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q2)

Financiación: info:eu-repo/grantAgreement/ES/CIBERObn/CB06-03-1012
Financiación: info:eu-repo/grantAgreement/ES/DGA/B16-20R
Financiación: info:eu-repo/grantAgreement/ES/DGA/E06-20R
Financiación: info:eu-repo/grantAgreement/ES/MCIU/RED2018-102471-T
Financiación: info:eu-repo/grantAgreement/ES/MICINN AEI/PID2019-104915RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-104379RB-C21-AEI-10.13039-501100011033

Tipo y forma: Article (Published version)

Área (Departamento): Área Química Inorgánica (Dpto. Química Inorgánica)
Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)