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The green tea polyphenol epigallocathechin\u20103\u2010gallate (<jats:styled-content style=\"fixed-case\">EGCG<\/jats:styled-content>) inhibits the growth of many types of cancer cells. We found that <jats:styled-content style=\"fixed-case\">EGCG<\/jats:styled-content> is selectively cytotoxic to <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>e cells with respect to normal mesothelial cells. <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>e cell viability was inhibited by predominant induction of apoptosis at lower doses and necrosis at higher doses. <jats:styled-content style=\"fixed-case\">EGCG<\/jats:styled-content> elicited H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> release in cell cultures, and exogenous catalase (<jats:styled-content style=\"fixed-case\">CAT<\/jats:styled-content>) abrogated <jats:styled-content style=\"fixed-case\">EGCG<\/jats:styled-content>\u2010induced cytotoxicity, apoptosis and necrosis. Confocal imaging of fluo 3\u2010loaded, <jats:styled-content style=\"fixed-case\">EGCG<\/jats:styled-content>\u2010exposed <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>e cells showed significant [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> rise, prevented by <jats:styled-content style=\"fixed-case\">CAT<\/jats:styled-content>, dithiothreitol or the T\u2010type Ca<jats:sup>2+<\/jats:sup> channel blockers mibefradil and NiCl<jats:sub>2<\/jats:sub>. Cell loading with dihydrorhodamine 123 revealed <jats:styled-content style=\"fixed-case\">EGCG<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> production, prevented by <jats:styled-content style=\"fixed-case\">CAT<\/jats:styled-content>, mibefradil or the Ca<jats:sup>2+<\/jats:sup> chelator <jats:styled-content style=\"fixed-case\">BAPTA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">AM<\/jats:styled-content>. Direct exposure of cells to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> produced similar effects on Ca<jats:sup>2+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>, and these effects were prevented by the same inhibitors. Sensitivity of <jats:styled-content style=\"fixed-case\">REN<\/jats:styled-content> cells to <jats:styled-content style=\"fixed-case\">EGCG<\/jats:styled-content> was correlated with higher expression of Ca<jats:sub>v<\/jats:sub>3.2 T\u2010type Ca<jats:sup>2+<\/jats:sup> channels in these cells, compared to normal mesothelium. Also, Ca<jats:sub>v<\/jats:sub>3.2 si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> on <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>e cells reduced <jats:italic>in vitro <\/jats:italic><jats:styled-content style=\"fixed-case\">EGCG<\/jats:styled-content> cytotoxicity and abated apoptosis and necrosis. Intriguingly, Ca<jats:sub>v<\/jats:sub>3.2 expression was observed in malignant pleural mesothelioma biopsies from patients, but not in normal pleura. In conclusion, data showed the expression of T\u2010type Ca<jats:sup>2+<\/jats:sup> channels in <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>e tissue and their role in <jats:styled-content style=\"fixed-case\">EGCG<\/jats:styled-content> selective cytotoxicity to <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>e cells, suggesting the possible use of these channels as a novel <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>e pharmacological target.<\/jats:p>","DOI":"10.1111\/j.1582-4934.2012.01584.x","type":"journal-article","created":{"date-parts":[[2012,5,5]],"date-time":"2012-05-05T12:45:15Z","timestamp":1336221915000},"page":"2667-2678","source":"Crossref","is-referenced-by-count":42,"title":["Epigallocatechin\u20103\u2010gallate induces mesothelioma cell death <i>via<\/i> H<sub>2<\/sub>O<sub>2<\/sub>\u2212dependent T\u2010type Ca<sup>2+<\/sup> channel 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