Assessment Effects of Resveratrol on Human Telomerase Reverse Transcriptase Messenger Ribonucleic Acid Transcript in Human Glioblastoma

Document Type : Original Article

Authors
Azin Mirzazadeh 1
Majid Kheirollahi 2
Ehsan Farashahi 3
Fatemeh Sadeghian-Nodoushan 4
Mohammad Hasan Sheikhha 3
Behrouz Aflatoonian 4
1 Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2 Department of Medical Genetics, Pediatrics Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Medical Genetics; Research and Clinical Centre for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
4 Stem Cell Biology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Abstract
Background: Glioblastoma (GBM) is the most common and aggressive brain tumor, which has a poor prognosis despite the advent of different therapeutic strategies. There are numerous molecular biomarkers to contribute diagnosis, prognosis, and prediction of response to the current therapy in GBM. One of the most important markers that are potentially valuable is immortalization-specific or immortalization-associated marker named “hTERT messenger ribonucleic acid (mRNA)” the key subunit of telomerase enzyme, which is expressed in more than 85% of cancer cells, in spite of the majority of normal somatic cells. In this study, we investigated the effects of resveratrol (RSV) on this mRNA marker level, leading to cancer progression. Materials and Methods: U-87MG cell line was obtained from Pasteur Institute of Iran and treated with various concentrations of 0–160 μg/mL of RSV and at different time points (24, 48, and 72 h). To evaluate viability of U-87MG cells, standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed. Real-time polymerase chain reaction (RT-PCR) was used for comparative and quantitative assessment of human telomerase reverse transcriptase (hTERT) mRNA copy number versus control–untreated group. Results: The results of our investigation suggested that RSV effectively inhibited cell growth and caused cell death in dose-dependent (P < 0.05) and not in time-dependent manner (P > 0.05), in vitro. Interestingly, quantitative RT-PCR analysis demonstrated that at half inhibition concentration, RSV dramatically decreased mRNA expression of hTERT, the catalytic subunit of telomerase enzyme, which leads to prevention of cell division and tumor progression. Conclusion: With regard to downregulation of this immortalization-associated marker, RSV may potentially be used as a therapeutic agent against GBM.

Keywords

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Advanced Biomedical Research
Volume 2017, june
June 2017
Pages 1-6