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

Paolini A, Curti V, Pasi F, Mazzini G, Nano R, Capelli E - Int. J. Oncol. (2015)

Bottom Line: The anticancer effect of this drug has been based on its antioxidant effects.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.Thus, the key for GA to induce a specific anticancer action is to use an optimal concentration that avoids these twin effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology and Biotechnology, Laboratory of Neuro Radio Experimental Biology, 'Lazzaro Spallanzani', University of Pavia, 27100 Pavia, Italy.

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.

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Related in: MedlinePlus

(A) Cell proliferation and (B) clonogenic ability of surviving cells. T98G cells were treated for 24 h with gallic acid and subsequently maintained in complete medium without the drug. Clone forming ability of T98G cell was assessed 12 days after the end of treatment. The results are normalized with the unexposed control (***P<0.05, *P<0.001).
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f2-ijo-46-04-1491: (A) Cell proliferation and (B) clonogenic ability of surviving cells. T98G cells were treated for 24 h with gallic acid and subsequently maintained in complete medium without the drug. Clone forming ability of T98G cell was assessed 12 days after the end of treatment. The results are normalized with the unexposed control (***P<0.05, *P<0.001).

Mentions: In the first phase of the investigation, the toxic effects of gallic acid were studied using MTT proliferation test, mitotic index and clonogenic assay. T98G cells were treated for 24 h with increasing concentrations of GA, ranging from 1 to 100 μg/ml. The toxic effect was evaluated determining the decrease in survival percentage (Fig. 1A) and MAI percentage (Fig. 1B) in comparison with the untreated samples. The results, summarized in Fig. 1, showed a toxic effect of GA in a concentration-dependent manner that reaches the highest value at the conditions of 50 and 100 g/ml. This highest value is correlated to a decrease in surviving cells 12 and 45%, respectively (P<0.01) and to a reduced mitotic index of 84 and 95% at the same concentrations (P<0.01). Considering cell proliferation, the maximum effect is observed after 72 h of consecutive GA treatment with a proliferation reduction of 45% at concentration of 100 μg/ml (Fig. 2A). To evaluate the capacity to repair damage induced by GA treatment, a colony forming assay was performed after the treatments. It was possible to observe that the number of colonies is progressively reduced with the increasing concentration of GA and for cells treated with the highest concentration the clonogenic capacity is completely compromised (Fig. 2B).


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

Paolini A, Curti V, Pasi F, Mazzini G, Nano R, Capelli E - Int. J. Oncol. (2015)

(A) Cell proliferation and (B) clonogenic ability of surviving cells. T98G cells were treated for 24 h with gallic acid and subsequently maintained in complete medium without the drug. Clone forming ability of T98G cell was assessed 12 days after the end of treatment. The results are normalized with the unexposed control (***P<0.05, *P<0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356495&req=5

f2-ijo-46-04-1491: (A) Cell proliferation and (B) clonogenic ability of surviving cells. T98G cells were treated for 24 h with gallic acid and subsequently maintained in complete medium without the drug. Clone forming ability of T98G cell was assessed 12 days after the end of treatment. The results are normalized with the unexposed control (***P<0.05, *P<0.001).
Mentions: In the first phase of the investigation, the toxic effects of gallic acid were studied using MTT proliferation test, mitotic index and clonogenic assay. T98G cells were treated for 24 h with increasing concentrations of GA, ranging from 1 to 100 μg/ml. The toxic effect was evaluated determining the decrease in survival percentage (Fig. 1A) and MAI percentage (Fig. 1B) in comparison with the untreated samples. The results, summarized in Fig. 1, showed a toxic effect of GA in a concentration-dependent manner that reaches the highest value at the conditions of 50 and 100 g/ml. This highest value is correlated to a decrease in surviving cells 12 and 45%, respectively (P<0.01) and to a reduced mitotic index of 84 and 95% at the same concentrations (P<0.01). Considering cell proliferation, the maximum effect is observed after 72 h of consecutive GA treatment with a proliferation reduction of 45% at concentration of 100 μg/ml (Fig. 2A). To evaluate the capacity to repair damage induced by GA treatment, a colony forming assay was performed after the treatments. It was possible to observe that the number of colonies is progressively reduced with the increasing concentration of GA and for cells treated with the highest concentration the clonogenic capacity is completely compromised (Fig. 2B).

Bottom Line: The anticancer effect of this drug has been based on its antioxidant effects.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.Thus, the key for GA to induce a specific anticancer action is to use an optimal concentration that avoids these twin effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology and Biotechnology, Laboratory of Neuro Radio Experimental Biology, 'Lazzaro Spallanzani', University of Pavia, 27100 Pavia, Italy.

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.

Show MeSH
Related in: MedlinePlus