title: Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells.
abstract: Malignant mesothelioma (MMe) is a poor-prognosis tumor in need of innovative therapies. In a previous in vivo study, we showed synergistic anti-MMe properties of the ascorbate/epigallocatechin-3-gallate/gemcitabine combination. We have now focused on the mechanism of action, showing the induction of apoptosis and cell cycle arrest through measurements of caspase 3, intracellular Ca(2+), annexin V, and DNA content. StellArray™ PCR technology and Western immunoblotting revealed DAPK2-dependent apoptosis, upregulation of cell cycle promoters, downregulation of cell cycle checkpoints and repression of NFκB expression. The complex of data indicates that the mixture is synergistic in inducing cell cycle deregulation and non-inflammatory apoptosis, suggesting its possible use in MMe treatment.
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale "Amedeo Avogadro", viale T. Michel 11, 15121 Alessandria, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Martinotti
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale "Amedeo Avogadro", viale T. Michel 11, 15121 Alessandria, Italy. Electronic address: ranzato@unipmn.it.
authors.forename: Elia
authors.initials: E
authors.lastname: Ranzato
authors.affiliation: IRCCS A.O.U. S. Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy; DI.ME.S., Università degli Studi di Genova, Via L. Alberti 2, 16132 Genova, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Parodi
authors.affiliation: IRCCS A.O.U. S. Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Vitale
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale "Amedeo Avogadro", viale T. Michel 11, 15121 Alessandria, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Burlando
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001205:Ascorbic Acid / Q000008:administration & dosage*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D004338:Drug Combinations; D003841:Deoxycytidine; D002392:Catechin; C045651:epigallocatechin gallate; D001205:Ascorbic Acid; D000093542:Gemcitabine
keywords: Cell cycle; Combined therapy; DAPK2; PCR array; REN mesothelioma cells