EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells

Our plain-English summary of EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells, by A. Demiroglu-Zergeroglu, G. Candemir, E. Turhanlar, et al (Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie, 2016).

The study

• Authors: A. Demiroglu-Zergeroglu, G. Candemir, E. Turhanlar, F. Sagir, N. Ayvali
• Journal: Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
• Published: 2016;84:2000-2007
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The unrestrained EGFR signalling contributes to malignant phenotype in a number of cancers including Malignant Mesotheliomas. Present study was designed to evaluate EGFR-dependent anti-proliferative and apoptotic effects of Gallic acid in transformed Mesothelial (MeT-5A) and Malignant Mesothelioma (SPC212) cells. Gallic acid reduced the viability of Malignant Mesothelioma cells in a concentration and time-dependent manner. However, viability of mesothelial cells reduced only at high concentration and longer time periods. Gallic acid restrained the activation of EGFR, ERK1/2 and AKT proteins and down regulated expression of Cyclin D and Bcl-2 genes, but upregulated the expression of p21 gene in EGF-induced SPC212 cells. GA-induced transitory G1 arrest and triggered mitochondrial and death receptor mediated apoptosis, which requires p38MAPK activation. The data provided here indicate that GA is able to inhibit EGFR dependent proliferation and survival signals and induces p38 pathway dependent apoptosis in Malignant Mesothelioma cells. On the basis of these experimental findings it is worthwhile to investigate further the biological activity of Gallic acid on other Mesothelioma cell lines harbouring aberrant EGFR signals.

Copyright © 2016 Elsevier Masson SAS. All rights reserved.

In plain English

This laboratory study used cells grown in dishes, not people, and did not study asbestos exposure. The authors tested gallic acid, a plant compound found in many fruits and drinks, on one malignant mesothelioma cell line (SPC212) and one transformed mesothelial cell line (MeT-5A). Gallic acid reduced mesothelioma cell viability more as concentration and time increased. The mesothelial cells were significantly affected only at the highest concentration tested. In a four-day comparison at one middle concentration, it reduced mesothelioma cell viability but not mesothelial cell viability. In mesothelioma cells stimulated with the growth factor EGF, gallic acid reduced activation of signalling proteins EGFR, ERK1/2 and AKT, but not STAT proteins. It lowered Cyclin D and Bcl-2 gene expression by 50% at 6 hours and temporarily held cells in the G1 phase of the cell cycle. It also increased the activity of caspase-8 and caspase-9, enzymes of programmed cell death. A p38 blocker, but not a JNK blocker, significantly reduced this effect. The authors concluded that gallic acid can inhibit EGFR-dependent signals and induce p38-dependent cell death in mesothelioma cells.

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) cell culture experiment
• Who was studied: Two cell lines: transformed mesothelial cells (MeT-5A, obtained from ATCC) and malignant mesothelioma cells (SPC212, gifted by the University of Fribourg, Switzerland). Most mechanism experiments used SPC212 cells only.
• Exposure: Gallic acid at four concentrations, printed as 50, 75, 100 and 200 mM, for up to 96 hours. No asbestos or other fiber exposure was studied.
• Main results:
  • In SPC212 mesothelioma cells, viability decreased with higher gallic acid concentration and longer treatment time.
  • MeT-5A mesothelial cells were significantly affected only at the highest concentration, printed as 200 mM.
  • At the concentration printed as 75 mM over 4 days, gallic acid reduced the viability of SPC212 cells but not of MeT-5A cells.
  • In EGF-stimulated SPC212 cells, gallic acid decreased phosphorylation (activation) of EGFR, ERK1/2 and AKT but not of STAT proteins.
  • In EGF-stimulated SPC212 cells, gallic acid raised phosphorylation of p38 but not of JNK.
  • In EGF-stimulated SPC212 cells, Cyclin D and Bcl-2 gene expression fell by 50% at 6 hours compared with untreated cells.
  • In the same cells, p21 gene expression rose in the first 3 hours and then returned to control levels.
  • Treated SPC212 cells accumulated in the G1 phase from 3 hours. The sub-G1 fraction increased over time, which the authors took to suggest cell death.
  • In SPC212 cells, gallic acid increased caspase-8 and caspase-9 enzyme activation at 24 hours compared with untreated cells.
  • Gallic acid-induced caspase-8 and caspase-9 dependent apoptosis was significantly reduced by pre-treatment with the p38 inhibitor SB203580 but not by the JNK inhibitor SP600125.
• The authors' conclusion: The authors concluded that gallic acid can inhibit EGFR-dependent proliferation and survival signals and induce p38 pathway dependent apoptosis in malignant mesothelioma cells. They considered it worthwhile to study gallic acid further in other mesothelioma cell lines with aberrant EGFR signals.
• Limitations the authors state:
  • The authors attributed an apparent increase in pERK with 100 uM of the comparison EGFR inhibitor CL at 24 hours to an experimental 'glitch', because other experimental sets did not show it.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: EGFR, Apoptosis, Malignant Mesothelioma, Mesothelial Cells, Mesothelioma.

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