Gallic acid exerts a protective or an anti-proliferative effect on glioma T98G cells via dose-dependent epigenetic regulation mediated by miRNAs

Abstract

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adulthood, characterized by very high recurrence. Following the limited results for conventional therapies, novel therapeutic agents are under investigation. Among the putative new molecules, gallic acid (GA) represents a promising new anticancer drug. The anticancer effect of this drug has been based on its antioxidant effects. The aim of the present study was to investigate the toxic effects of GA on the T98G human glioblastoma cell line and its capacity to modulate the expression of microRNAs targeting the genes involved in tumor growth and invasion. Cytotoxicity, clonogenic ability and cell migration after GA treatment were tested. Moreover, the expression of miRNAs that target genes for antioxidant mitochondrial enzymes (miR-17-3p), p-21 protein (miR-21-5p) and ATM (miR-421-5p) was determined by qRT-PCR. The results confirmed in the T98G cells the anti-proliferative effect of GA reported for other glioma cell lines and showed that the miRNA expression changes depending on GA concentrations. Different GA concentrations can determine a protective or a toxic effect on tumor cells. Thus, the key for GA to induce a specific anticancer action is to use an optimal concentration that avoids these twin effects.

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

“…It has been demonstrated that gallic acid can block the growth of DU-145 cells at G2/M phases of cell cycle (24). Therefore, in our study, the reduction of viability and proliferation in DU-145 cells, at least in part, may be as a result of anti-proliferative effects of gallic acid that was reported for glioma cell lines in previous study (26). In our study, gallic acid decreased the synthesis of IL-6 in DU-145 cells in dose-dependent manner (Figure 4).…”

Recent Advances in Anticancer Activities and Drug Delivery Systems of Tannins

“…GTs are hydrolyzed to GA before being metabolized to methylated derivatives . GA has shown anticancer activity against a variety of cell lineages, including oral, leukemia, glioblastoma multiforme, prostate, breast, chondrosarcoma, cervical cancer, and so on. Multitargeted molecular mechanisms via the modulation of genes that encode for cell cycle, metastasis, angiogenesis, and apoptosis have been revealed for the cancer therapeutic activity of GA .…”

Antimicrobial activity and cytotoxic assessment of gallic and ellagic acids

“…Some important pharmacological activities have already been described for gallic acid, such as antioxidant and antiinflammatory properties (YANG et al, 2015), antimutagenic and anticarcinogenic properties (LEE; HARRISON; GRINSTEIN, 2003;LU et al, 2010;PAOLINI et al, 2015). For ellagic acid, the following activities have been described: anticarcinogenic, hepatoprotective, DNA inhibitor topoisomerase (VATTEM et al, 2005;AGGARWAL;SHISHODIA, 2006;CORTAZAR;COOMBS;WALKER, 2007), antioxidant (DEVIPRIYA et al, 2007), anti-inflamatory (YUCE et al, 2007PAPOUTSI et al, 2008) and gastroprotective activities (IINO et al, 2001).…”