title: Oleuropein-Enriched Olive Leaf Extract Affects Calcium Dynamics and Impairs Viability of Malignant Mesothelioma Cells.
abstract: Malignant mesothelioma is a poor prognosis cancer in urgent need of alternative therapies. Oleuropein, the major phenolic of olive tree (Olea europaea L.), is believed to have therapeutic potentials for various diseases, including tumors. We obtained an oleuropein-enriched fraction, consisting of 60% w/w oleuropein, from olive leaves, and assessed its effects on intracellular Ca(2+) and cell viability in mesothelioma cells. Effects of the oleuropein-enriched fraction on Ca(2+) dynamics and cell viability were studied in the REN mesothelioma cell line, using fura-2 microspectrofluorimetry and MTT assay, respectively. Fura-2-loaded cells, transiently exposed to the oleuropein-enriched fraction, showed dose-dependent transient elevations of cytosolic Ca(2+) concentration ([Ca(2+)]i). Application of standard oleuropein and hydroxytyrosol, and of the inhibitor of low-voltage T-type Ca(2+) channels NNC-55-0396, suggested that the effect is mainly due to oleuropein acting through its hydroxytyrosol moiety on T-type Ca(2+) channels. The oleuropein-enriched fraction and standard oleuropein displayed a significant antiproliferative effect, as measured on REN cells by MTT cell viability assay, with IC50 of 22 μg/mL oleuropein. Data suggest that our oleuropein-enriched fraction from olive leaf extract could have pharmacological application in malignant mesothelioma anticancer therapy, possibly by targeting T-type Ca(2+) channels and thereby dysregulating intracellular Ca(2+) dynamics.
authors.affiliation: Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Via De Marini 6, 16149 Genova, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Marchetti
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica (DISIT), Università del Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Clericuzio
authors.affiliation: Dipartimento di Scienze della Terra dell'Ambiente e della Vita (DISTAV), Università degli Studi di Genova, Corso Europa 26, 16132 Genova, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Borghesi
authors.affiliation: Dipartimento di Scienze della Terra dell'Ambiente e della Vita (DISTAV), Università degli Studi di Genova, Corso Europa 26, 16132 Genova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cornara
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica (DISIT), Università del Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ribulla
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica (DISIT), Università del Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Gosetti
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica (DISIT), Università del Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Marengo
authors.affiliation: Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Via De Marini 6, 16149 Genova, Italy ; Dipartimento di Scienze e Innovazione Tecnologica (DISIT), Università del Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Burlando