title: Cellular determinants involving mitochondrial dysfunction, oxidative stress and apoptosis correlate with the synergic cytotoxicity of epigallocatechin-3-gallate and menadione in human leukemia Jurkat T cells.
abstract: We have investigated the growth-suppressive action of epigallocatechin-3-gallate (EGCG) on human leukemia Jurkat T cells. Results show a strong correlation between the dose-dependent reduction of clonogenic survival following acute EGCG treatments and the EGCG-induced decline of the mitochondrial level of Ca(2+). The cell killing ability of EGCG was synergistically enhanced by menadione. In addition, the cytotoxic effect of EGCG applied alone or in combination with menadione was accompanied by apoptosis induction. We also observed that in acute treatments EGCG displays strong antioxidant properties in the intracellular milieu, but concurrently triggers some oxidative stress generating mechanisms that can fully develop on a longer timescale. In parallel, EGCG dose-dependently induced mitochondrial depolarization during exposure, but this condition was subsequently reversed to a persistent hyperpolarized mitochondrial state that was dependent on the activity of respiratory Complex I. Fluorimetric measurements suggest that EGCG is a mitochondrial Complex III inhibitor and indicate that EGCG evokes a specific cellular fluorescence with emission at 400nm and two main excitation bands (at 330nm and 350nm) that may originate from a mitochondrial supercomplex containing dimeric Complex III and dimeric ATP-synthase, and therefore could provide a valuable means to characterize the functional properties of the respiratory chain.
authors.affiliation: "Carol Davila" University of Medicine and Pharmacy, Dept. of Biophysics, 8 Eroii Sanitari, 050474 Bucharest, Romania.
authors.forename: Ioana Teodora
authors.initials: IT
authors.lastname: Tofolean
authors.affiliation: "Carol Davila" University of Medicine and Pharmacy, Dept. of Biophysics, 8 Eroii Sanitari, 050474 Bucharest, Romania.
authors.forename: Constanta
authors.initials: C
authors.lastname: Ganea
authors.affiliation: "Carol Davila" University of Medicine and Pharmacy, Dept. of Biophysics, 8 Eroii Sanitari, 050474 Bucharest, Romania.
authors.forename: Diana
authors.initials: D
authors.lastname: Ionescu
authors.affiliation: "Carol Davila" University of Medicine and Pharmacy, Dept. of Biophysics, 8 Eroii Sanitari, 050474 Bucharest, Romania.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Filippi
authors.affiliation: "Carol Davila" University of Medicine and Pharmacy, Dept. of Biophysics, 8 Eroii Sanitari, 050474 Bucharest, Romania.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Garaiman
authors.affiliation: "Carol Davila" University of Medicine and Pharmacy, Dept. of Biophysics, 8 Eroii Sanitari, 050474 Bucharest, Romania.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Goicea
authors.affiliation: "Carol Davila" University of Medicine and Pharmacy, Dept. of Biophysics, 8 Eroii Sanitari, 050474 Bucharest, Romania.
authors.forename: Mihnea-Alexandru
authors.initials: MA
authors.lastname: Gaman
authors.affiliation: "Carol Davila" University of Medicine and Pharmacy, Dept. of Biophysics, 8 Eroii Sanitari, 050474 Bucharest, Romania.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Dimancea
authors.affiliation: "Carol Davila" University of Medicine and Pharmacy, Dept. of Biophysics, 8 Eroii Sanitari, 050474 Bucharest, Romania. Electronic address: virbaran@yahoo.com.
authors.forename: Irina
authors.initials: I
authors.lastname: Baran
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D024483:Vitamin K 3 / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D024483:Vitamin K 3; D002392:Catechin; C045651:epigallocatechin gallate; D002118:Calcium
keywords: Antimycin A (PubChem CID: 14957); Apoptosis; Cyclosporin A (PubChem CID: 5284373); Epigallocatechin-3-gallate; Epigallocatechin-3-gallate (PubChem CID: 65064); Leukemia; Menadione; Menadione sodium bisulfite (PubChem CID: 23665888); Mitochondrial dysfunction; Oxidative stress; Rotenone (PubChem CID: 6758)