Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0046749
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dc.title(-)-Epigallocatechin-3-Gallate Induces Non-Apoptotic Cell Death in Human Cancer Cells via ROS-Mediated Lysosomal Membrane Permeabilization
dc.contributor.authorZhang, Y.
dc.contributor.authorYang, N.-D.
dc.contributor.authorZhou, F.
dc.contributor.authorShen, T.
dc.contributor.authorDuan, T.
dc.contributor.authorZhou, J.
dc.contributor.authorShi, Y.
dc.contributor.authorZhu, X.-Q.
dc.contributor.authorShen, H.-M.
dc.date.accessioned2014-11-26T02:11:51Z
dc.date.available2014-11-26T02:11:51Z
dc.date.issued2012-10-08
dc.identifier.citationZhang, Y., Yang, N.-D., Zhou, F., Shen, T., Duan, T., Zhou, J., Shi, Y., Zhu, X.-Q., Shen, H.-M. (2012-10-08). (-)-Epigallocatechin-3-Gallate Induces Non-Apoptotic Cell Death in Human Cancer Cells via ROS-Mediated Lysosomal Membrane Permeabilization. PLoS ONE 7 (10) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0046749
dc.identifier.issn19326203
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/108705
dc.description.abstract(-)-Epigallocatechin-3-gallate (EGCG) is the most extensive studied tea polyphenol for its anti-cancer function. In this study, we report a novel mechanism of action for EGCG-mediated cell death by identifying the critical role of lysosomal membrane permeabilization (LMP). First, EGCG-induced cell death in human cancer cells (both HepG2 and HeLa) was found to be caspase-independent and accompanied by evident cytosolic vacuolization, only observable when cells were treated in serum-free medium. The cytosolic vacuolization observed in EGCG-treated cells was most probably caused by lysosomal dilation. Interestingly, EGCG was able to disrupt autophagic flux at the degradation stage by impairment of lysosomal function, and EGCG-induced cell death was independent of Atg5 or autophagy. The key finding of this study is that EGCG is able to trigger LMP, as evidenced by Lyso-Tracker Red staining, cathepsin D cytosolic translocation and cytosolic acidification. Consistently, a lysosomotropic agent, chloroquine, effectively rescues the cell death via suppressing LMP-caused cytosolic acidification. Lastly, we found that EGCG promotes production of intracellular ROS upstream of LMP and cell death, as evidenced by increased level of ROS in cells treated with EGCG and the protective effects of antioxidant N-acetylcysteine (NAC) against EGCG-mediated LMP and cell death. Taken together, data from our study reveal a novel mechanism underlying EGCG-induced cell death involving ROS and LMP. Therefore, understanding this lysosome-associated cell death pathway shed new lights on the anti-cancer effects of EGCG. © 2012 Zhang et al.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1371/journal.pone.0046749
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentSAW SWEE HOCK SCHOOL OF PUBLIC HEALTH
dc.description.doi10.1371/journal.pone.0046749
dc.description.sourcetitlePLoS ONE
dc.description.volume7
dc.description.issue10
dc.description.page-
dc.identifier.isiut000309831500069
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