RT journal article
T1 Silver Clusters of Five Atoms as Highly Selective Antitumoral Agents Through Irreversible Oxidation of Thiols
A1 Porto, Vanesa
A1 Buceta, David
A1 Domínguez, Blanca
A1 Carneiro, Carmen
A1 Borrajo, Erea
A1 Fraile, María
A1 Davila-Ferreira, Nerea
A1 Arias, Iria R.
A1 Blanco, José M.
A1 Blanco, María C.
A1 Devida, Juan M.
A1 Giovanetti, Lisandro J.
A1 Requejo, Félix G.
A1 Hernández Garrido, Juan Carlos
A1 Calvino Gámez, José Juan
A1 López Haro, Miguel
A1 Barone, Giampaolo
A1 James, Andrew M.
A1 García-Caballero, Tomás
A1 González-Castaño, Diego M.
A1 Treder, Martin
A1 Huber, Wolfgang
A1 Vidal, Anxo
A1 Murphy, Michael P.
A1 López-Quintela, M. Arturo
A1 Domínguez, Fernando
A2 Ciencia de los Materiales e Ingeniería Metalúrgica y Química Inorgánica
AB Low atomicity clusters present properties dependent on the size, due to the quantum confinement, with well-defined electronic structures and high stability. Here it is shown that Ag-5 clusters catalyze the complete oxidation of sulfur to S+6. Ag-5 catalytic activity increases with different oxidant species in the order O-2 MUCH LESS-THAN H2O2 < OH center dot. Selective oxidation of thiols on the cysteine residues of glutathione and thioredoxin is the primary mechanism human cells have to maintain redox homeostasis. Contingent upon oxidant concentration, Ag-5 catalyzes the irreversible oxidation of glutathione and thioredoxin, triggering apoptosis. Modification of the intracellular environment to a more oxidized state to mimic conditions within cancer cells through the expression of an activated oncogene (HRAS(G12V)) or through ARID1A mutation, sensitizes cells to Ag-5 mediated apoptosis. While cancers evolve to evade treatments designed to target pathways or genetic mutations that drive them, they cannot evade a treatment that takes advantage of aberrant redox homeostasis, which is essential for tumor progression and metastasis. Ag-5 has antitumor activity in mice with orthotopic lung tumors reducing primary tumor size, and the burden of affected lymphatic nodes. The findings suggest the unique intracellular redox chemistry of Ag-5 may lead to new redox-based approaches to cancer therapy.
PB WILEY
SN 1616-301X
YR 2022
FD 2022-03
LK http://hdl.handle.net/10498/27244
UL http://hdl.handle.net/10498/27244
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 15-nov-2026