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

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• 作者：Ioana Teodora Tofolean ; Constanta Ganea ; Diana Ionescu ; Alexandru Filippi ; Alexandru Garaiman ; Alexandru Goicea ; Mihnea-Alexandru Gaman ; Alexandru Dimancea ; Irina Baran ; ^{virbaran@yahoo.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Epigallocatechin-3-gallate (PubChem CID ; 65064) ; Menadione sodium bisulfite (PubChem CID ; 23665888) ; Cyclosporin A (PubChem CID ; 5284373) ; Antimycin A (PubChem CID ; 14957) ; Rotenone (PubChem CID ; 6758)
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：103
• 期：Complete
• 页码：300-317
• 全文大小：6127 K

文摘

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 Ca²⁺. 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 400 nm and two main excitation bands (at 330 nm and 350 nm) 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.