EGCG induces human mesothelioma cell death by inducing reactive oxygen species and autophagy

Our plain-English summary of EGCG induces human mesothelioma cell death by inducing reactive oxygen species and autophagy, by M. Satoh, Y. Takemura, H. Hamada, et al (Cancer Cell International, 2013).

The study

• Authors: M. Satoh, Y. Takemura, H. Hamada, Y. Sekido, S. Kubota
• Journal: Cancer Cell International
• Published: 2013;13(1):19
• Cited by: 58 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. We studied whether a green tea polyphenol, epigallocathechin-3-gallate (EGCG), could induce cell death in five human mesothelioma cell lines. We found that EGCG induced apoptosis in all five mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism. EGCG induced reactive oxygen species (ROS), and impaired the mitochondrial membrane potential. As treatment with ROS scavengers, catalase and tempol, significantly inhibited the EGCG-induced apoptosis, ROS is considered to be responsible for the EGCG-induced apoptosis. Further, we found that EGCG induced autophagy, and that when autophagy was suppressed by chloroquine, the EGCG-induced cell death was enhanced. Taken together, these results suggest that EGCG has a great potential for the treatment of mesothelioma by inducing apoptosis and autophagy.

In plain English

This was a laboratory study of human mesothelioma cells grown in culture. No patients or animals were studied, and asbestos itself was not tested. The authors treated five mesothelioma cell lines for 24 hours with EGCG, a compound from green tea, at 10 to 500 μM. EGCG reduced cell survival in a dose-dependent way. The concentration needed to cut growth by half ranged from 29 μM (EHMES-1) to 179 μM (EHMES-10). Tests in four of the lines showed signs of apoptosis, a form of programmed cell death. In EHMES-10 cells, EGCG raised reactive oxygen species and lowered mitochondrial membrane potential. In the same cells, two agents that remove reactive oxygen species, catalase and tempol, reduced the cell death. Tempol's effect was significant at 200 and 300 μM EGCG but not at 50 or 100 μM. In three cell lines, EGCG also triggered autophagy, a process in which cells break down their own parts. In Y-meso cells, blocking autophagy with chloroquine increased cell death at 150 μM EGCG but not at 100 μM. The authors concluded that EGCG may be useful for treating malignant mesothelioma, and said animal experiments were underway.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment on cultured human mesothelioma cell lines
• Who was studied: Five human mesothelioma cell lines: EHMES-10, EHMES-1, ACC-meso, Y-meso and MSTO-211H. Most mechanism experiments used EHMES-10 cells.
• Exposure: EGCG (epigallocatechin-3-gallate, a green tea polyphenol) at 10 to 500 μM for 24 hours. Some experiments added catalase, tempol or chloroquine. No asbestos exposure was studied.
• Main results:
  • EGCG reduced cell viability in all five lines in a dose-dependent manner. The concentrations needed to inhibit growth by 50% were 179 μM (EHMES-10), 29 μM (EHMES-1), 42 μM (ACC-meso), 128 μM (Y-meso) and 35 μM (MSTO-211H).
  • The TUNEL test showed apoptosis in four cell lines: EHMES-10, EHMES-1, ACC-meso and Y-meso.
  • EHMES-10 cells were treated with 100, 250 and 500 μM EGCG. The share of cells with normal mitochondrial membrane potential fell to 91.88%, 59.12% and 14.26%, respectively.
  • At the same doses (100, 250 and 500 μM), the share of EHMES-10 cells with low mitochondrial membrane potential rose to 5.58%, 35.96% and 82.7%, respectively.
  • In EHMES-10 cells, catalase significantly prevented EGCG-induced cell death.
  • In EHMES-10 cells, tempol significantly inhibited cell death caused by 200 or 300 μM EGCG, but not by 50 or 100 μM EGCG.
  • In ACC-meso, Y-meso and EHMES-10 cells, EGCG increased levels of LC3-II, a marker of autophagy, at 3 and 6 hours after treatment.
  • In Y-meso cells, chloroquine at 5 and 10 μM increased cell death caused by 150 μM EGCG. It did not change cell death caused by 100 μM EGCG.
• The authors' conclusion: The authors concluded that EGCG may be useful for treating malignant mesothelioma. They reported that animal experiments combining EGCG with chloroquine were underway to confirm the effects.
• Limitations the authors state:
  • The authors did not examine H2O2-dependent T-type calcium channel opening, a mechanism reported by another group. It is therefore unclear whether that mechanism played a part in their results.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Reactive Oxygen Species (ROS), Malignant Mesothelioma, Apoptosis.

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