The anticancer effect related to disturbances in redox balance on Caco-2 cells caused by an alkynyl gold(I) complex

Sánchez-de-Diego, C. ; Mármol, I. ; Pérez, R. ; Gascón, S. (Universidad de Zaragoza) ; Rodriguez-Yoldi, M. (Universidad de Zaragoza) ; Cerrada, E. (Universidad de Zaragoza)

Resumen: The alkynyl gold(I) derivative Au(C=CPh)(PTA)] (PTA = 1, 3, 5-triaza-7-phosphaadamantane) induces apoptosis in colorectal carcinoma tumour cells (Caco-2) without affecting to normal enterocytes. Au(C=CPh)(PTA)] is a slight lipophilic drug, stable in PBS (Phosphate Buffered Saline) and able to bind BSA (Bovin Serum Albumin) by hydrophobic interactions. Once inside the cell, Au(C=CPh)(PTA)] targets seleno proteins such as Thioredoxin Reductase 1, increasing ROS (Reactive Oxygen Species) levels, reducing cell viability and proliferation and inducing mitochondrial apoptotic pathway, pro-apoptotic and anti-apoptotic protein imbalance, loss of mitochondrial membrane potential, cytochrome c release and activation of caspases 9 and 3. Moreover, unlike other metal-based drugs such as cisplatin, Au(C=CPh)(PTA)] does not target nucleic acid, reducing the risk of side mutation in the DNA. In consequence, our results predict a promising future for Au(C=CPh)(PTA)] as a chemotherapeutic agent for colorectal carcinoma.

Idioma: Inglés

DOI: 10.1016/j.jinorgbio.2016.11.009

Año: 2017

Publicado en: JOURNAL OF INORGANIC BIOCHEMISTRY 166 (2017), 108-121
ISSN: 0162-0134

Factor impacto JCR: 3.063 (2017)

Categ. JCR: CHEMISTRY, INORGANIC & NUCLEAR rank: 10 / 45 = 0.222 (2017) - Q1 - T1
Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 137 / 292 = 0.469 (2017) - Q2 - T2

Factor impacto SCIMAGO: 0.743 - Inorganic Chemistry (Q2) - Biochemistry (Q3)

Financiación: info:eu-repo/grantAgreement/ES/DGA/A32
Financiación: info:eu-repo/grantAgreement/ES/DGA/E104
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CB06-03-1012
Financiación: info:eu-repo/grantAgreement/ES/MINECO-FEDER/CTQ2013-48635-C2-1-P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2013-41651-R

Tipo y forma: Artículo (PostPrint)

Área (Departamento): Área Química Inorgánica (Dpto. Química Inorgánica)
Área (Departamento): Área Fisiología (Dpto. Farmacología y Fisiolog.)
Área (Departamento): Área Técnica. Lab. y Talleres (Dpto. Patología Animal)