title: EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells.
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.
authors.affiliation: Gebze Technical University, Department of Molecular Biology & Genetics, Gebze/Kocaeli, Turkey. Electronic address: ademiroglu@gtu.edu.tr.
authors.forename: Asuman
authors.initials: A
authors.lastname: Demiroglu-Zergeroglu
authors.affiliation: Gebze Technical University, Department of Molecular Biology & Genetics, Gebze/Kocaeli, Turkey.
authors.forename: Gulsife
authors.initials: G
authors.lastname: Candemir
authors.affiliation: Gebze Technical University, Department of Molecular Biology & Genetics, Gebze/Kocaeli, Turkey.
authors.forename: Ebru
authors.initials: E
authors.lastname: Turhanlar
authors.affiliation: Gebze Technical University, Department of Molecular Biology & Genetics, Gebze/Kocaeli, Turkey.
authors.forename: Fatma
authors.initials: F
authors.lastname: Sagir
authors.affiliation: Gebze Technical University, Department of Molecular Biology & Genetics, Gebze/Kocaeli, Turkey.
authors.forename: Nurettin
authors.initials: N
authors.lastname: Ayvali
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005707:Gallic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008654:Mesothelioma / Q000188:drug therapy / Q000378:metabolism*; D000086002:Mesothelioma, Malignant; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D005707:Gallic Acid; C512478:EGFR protein, human; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases
keywords: AKT; Caspases; EGFR; Gallic acid; MAPK; Mesothelioma