ArticlePloS one2012
(-)-Epigallocatechin-3-gallate induces non-apoptotic cell death in human cancer cells via ROS-mediated lysosomal membrane permeabilization.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 96 citations in OpenAlex.
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- Chitosan Nanoparticles Unlock the Antioxidant Potential of Epigallocatechin Gallate in Pancreatic and Hepatic Cancer Cell Models.ACS omega · 2026Article
- Recent Update Targeting Autophagy-Apoptosis Crosstalk Using Bioactive Natural Products for Ovarian Cancer Treatment.Biomedicines · 2026Review
- Lysosome-dependent cell death in hepatocellular carcinoma: unlocking the therapeutic potential of natural products.Frontiers in pharmacology · 2026Review
- Epigallocatechin gallate, folic acid, vitamin B12 and hyaluronic acid in the management of male Human Papilloma Virus Infection: A case series.SAGE open medical case reports · 2026Article
- LOX-1 and Its Splicing Variant LOX-1International journal of hepatology · 2026Article
- Anticancer Molecular Mechanisms of Epigallocatechin Gallate: An Updated Review on Clinical Trials.Food science & nutrition · 2025Review
- Molecular Evidence of the Bio-activities of Traditional Home Medicine Ingredients.Current topics in medicinal chemistry · 2025Review
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- Anticancer Activity of Benzo[Cells · 2024Article
- In Vitro Effect of Epigallocatechin Gallate on Heme Synthesis Pathway and Protoporphyrin IX Production.International journal of molecular sciences · 2024Article
- Breast cancer therapy: from the perspective of glucose metabolism and glycosylation.Molecular biology reports · 2024Review
- Synergistic inhibitory actions of resveratrol, epigallocatechin-3-gallate, and diallyl trisulfide against skin cancer cell line A431 through mitochondrial caspase dependent pathway: a combinational drug approach.Medical oncology (Northwood, London, England) · 2024Article
- Green tea polyphenol EGCg induces cell fusionBiochemistry and biophysics reports · 2023Article
- Preventing Persistence of HPV Infection with Natural Molecules.Pathogens (Basel, Switzerland) · 2023Review
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- Antitumour Effects of Selected Pyridinium Salts on Sensitive Leukaemia HL60 Cells and Their Multidrug Resistant Topoisomerase II-Defective HL60/MX2 Counterparts.Molecules (Basel, Switzerland) · 2022Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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