title: The anticancer effect related to disturbances in redox balance on Caco-2 cells caused by an alkynyl gold(I) complex.
abstract: 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.
authors.affiliation: Departamento de Farmacología y Fisiología. Unidad de Fisiología, Facultad de Veterinaria, Universidad de Zaragoza, 50013, Zaragoza, CIBERobn, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez-de-Diego
authors.affiliation: Departamento de Farmacología y Fisiología. Unidad de Fisiología, Facultad de Veterinaria, Universidad de Zaragoza, 50013, Zaragoza, CIBERobn, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Mármol
authors.affiliation: Departamento de Farmacología y Fisiología. Unidad de Fisiología, Facultad de Veterinaria, Universidad de Zaragoza, 50013, Zaragoza, CIBERobn, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Pérez
authors.affiliation: Departamento de Farmacología y Fisiología. Unidad de Fisiología, Facultad de Veterinaria, Universidad de Zaragoza, 50013, Zaragoza, CIBERobn, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Gascón
authors.affiliation: Departamento de Farmacología y Fisiología. Unidad de Fisiología, Facultad de Veterinaria, Universidad de Zaragoza, 50013, Zaragoza, CIBERobn, Spain. Electronic address: mjrodyol@unizar.es.
authors.forename: Mª Jesús
authors.initials: MJ
authors.lastname: Rodriguez-Yoldi
authors.affiliation: Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., 50009 Zaragoza, Spain. Electronic address: ecerrada@unizar.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Cerrada
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002417:Cattle; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D006046:Gold / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009363:Neoplasm Proteins / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000737:chemistry; D054481:Thioredoxin Reductase 1 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009363:Neoplasm Proteins; D012710:Serum Albumin, Bovine; D006046:Gold; D045304:Cytochromes c; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9
keywords: Alkynyl gold(I); Apoptosis; Caco-2 cells; Cytochrome c; Redox; Thioredoxin reductase