{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T08:15:08Z","timestamp":1784880908587,"version":"3.55.0"},"reference-count":40,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>Malignant mesothelioma is a poor prognosis cancer in urgent need of alternative therapies. Oleuropein, the major phenolic of olive tree (<jats:italic>Olea europaea<\/jats:italic>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<jats:sup>2+<\/jats:sup>and cell viability in mesothelioma cells. Effects of the oleuropein-enriched fraction on Ca<jats:sup>2+<\/jats:sup>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<jats:sup>2+<\/jats:sup>concentration (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:msub><mml:mrow><mml:mfenced open=\"[\" close=\"]\" separators=\"|\"><mml:mrow><mml:msup><mml:mrow><mml:mi mathvariant=\"normal\">C<\/mml:mi><mml:mi mathvariant=\"normal\">a<\/mml:mi><\/mml:mrow><mml:mrow><mml:mn mathvariant=\"normal\">2<\/mml:mn><mml:mo>+<\/mml:mo><\/mml:mrow><\/mml:msup><\/mml:mrow><\/mml:mfenced><\/mml:mrow><mml:mrow><mml:mi mathvariant=\"normal\">i<\/mml:mi><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>). Application of standard oleuropein and hydroxytyrosol, and of the inhibitor of low-voltage T-type Ca<jats:sup>2+<\/jats:sup>channels NNC-55-0396, suggested that the effect is mainly due to oleuropein acting through its hydroxytyrosol moiety on T-type Ca<jats:sup>2+<\/jats:sup>channels. The oleuropein-enriched fraction and standard oleuropein displayed a significant antiproliferative effect, as measured on REN cells by MTT cell viability assay, with IC<jats:sub>50<\/jats:sub>of 22\u2009<jats:italic>\u03bc<\/jats:italic>g\/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<jats:sup>2+<\/jats:sup>channels and thereby dysregulating intracellular Ca<jats:sup>2+<\/jats:sup>dynamics.<\/jats:p>","DOI":"10.1155\/2015\/908493","type":"journal-article","created":{"date-parts":[[2015,11,26]],"date-time":"2015-11-26T21:01:11Z","timestamp":1448571671000},"page":"1-9","source":"Crossref","is-referenced-by-count":31,"title":["Oleuropein-Enriched Olive Leaf Extract Affects Calcium Dynamics and Impairs Viability of Malignant Mesothelioma Cells"],"prefix":"10.1155","volume":"2015","author":[{"given":"Carla","family":"Marchetti","sequence":"first","affiliation":[{"name":"Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Via De Marini 6, 16149 Genova, 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