Gallic acid inhibits invasion and reduces IL-6 gene expression, PSTAT3, PERK1/2, and pAKT cellular signaling proteins in human prostate cancer DU-145 cells

Abstract

Background: Prostate cancer (PC) is a malignant disease, which is common in men. Interleukin-6 (IL-6) mediates the progression of PC through PI3K/AKT, JAK-STAT, and ERK1/2 MAPKs signaling pathways. Gallic acid, a phenolic compound, has anti-oxidant, anti-proliferative, and anti-tumorigenic properties. Objectives: This study was undertaken to evaluate the effects of gallic acid on DU-145 cell viability, proliferation, invasion, IL-6 gene expression, and the cellular levels of phosphorylated STAT3, ERK1/2, and AKT signaling proteins. Methods: DU-145 cells were treated with gallic acid (0 - 100 µM). The 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay was done in order to evaluate the cytotoxicity of gallic acid on DU-145 cells. IL-6 gene expression was investigated, using RT-qPCR. The levels of phosphorylated ERK1/2, AKT, and STAT3 signaling pathways were assessed by Western blotting technic. DU-145 cells invasion were measured by invasion assay test. Results: A significant reduction was observed in viability, proliferation, and invasion of DU-145 cells after treatment with gallic acid. Also, cellular levels of phosphorylated STAT3, ERK1/2, and AKT signaling proteins decreased after 48 hours in a dose-dependent manner by gallic acid. Secretion and gene expression of IL-6 were decreased in DU-145 cells treated with gallic acid. Conclusions: The results of this study showed that gallic acid can lead to a reduction in survival, proliferation, and invasion in DU-145 cell line by reducing protein IL-6 and its gene expression, pSTAT3, pERK1/2, and pAKT signaling protein pathways. Therefore, it seems that gallic acid can be regarded as a potent agent in the treatment of prostate cancer.