Epigallocatechin-3-gallate induces mesothelioma cell death via H2 O2 -dependent T-type Ca2+ channel opening.

Journal of Cellular and Molecular Medicine
Elia RanzatoBruno Burlando

Abstract

Malignant mesothelioma (MMe) is a highly aggressive, lethal tumour requiring the development of more effective therapies. The green tea polyphenol epigallocathechin-3-gallate (EGCG) inhibits the growth of many types of cancer cells. We found that EGCG is selectively cytotoxic to MMe cells with respect to normal mesothelial cells. MMe cell viability was inhibited by predominant induction of apoptosis at lower doses and necrosis at higher doses. EGCG elicited H(2) O(2) release in cell cultures, and exogenous catalase (CAT) abrogated EGCG-induced cytotoxicity, apoptosis and necrosis. Confocal imaging of fluo 3-loaded, EGCG-exposed MMe cells showed significant [Ca(2+) ](i) rise, prevented by CAT, dithiothreitol or the T-type Ca(2+) channel blockers mibefradil and NiCl(2) . Cell loading with dihydrorhodamine 123 revealed EGCG-induced ROS production, prevented by CAT, mibefradil or the Ca(2+) chelator BAPTA-AM. Direct exposure of cells to H(2) O(2) produced similar effects on Ca(2+) and ROS, and these effects were prevented by the same inhibitors. Sensitivity of REN cells to EGCG was correlated with higher expression of Ca(v) 3.2 T-type Ca(2+) channels in these cells, compared to normal mesothelium. Also, Ca(v) 3.2 siRNA on MM...Continue Reading

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Citations

Jun 25, 2013·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Fabian VandermeersLuc Willems
Dec 23, 2015·Evidence-based Complementary and Alternative Medicine : ECAM·Carla MarchettiBruno Burlando
Nov 27, 2019·Cancers·Simona MartinottiElia Ranzato
Jan 30, 2020·International Journal of Molecular Sciences·Simona MartinottiElia Ranzato
Feb 14, 2019·International Journal of Molecular Sciences·Simona MartinottiElia Ranzato
Apr 24, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Simona MartinottiElia Ranzato
Jul 31, 2020·Dose-response : a Publication of International Hormesis Society·Edward J CalabreseVittorio Calabrese
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May 22, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xinlei LiXinyi Jin
Aug 8, 2021·International Journal of Molecular Sciences·Malgorzata Chmielewska-Kassassir, Lucyna A Wozniak

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Methods Mentioned

BETA
Protein Assay
PCR
Transfection
biopsy
confocal microscopy
Fluorescence

Software Mentioned

Instat
Scion Image
GraphPad
Zeiss LSM 510

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