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

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.

Resveratrol-Mediated Regulation of Mitochondria Biogenesis-associated Pathways in Neurodegenerative Diseases: Molecular Insights and Potential Therapeutic Applications

“…An opposite effect has been observed in different cancer cell lines where resveratrol reduces TERT and induces cellular apoptosis [ 176 , 177 ]. Resveratrol also inhibits the expression of TERT in metastatic glioblastom cancer cells, a phenomenon associated with dose-dependent prevention of cell proliferation and tumor regression [ 178 ]. Data on resveratrol-enhanced mitochondrial biogenesis through TERT are still limited, especially regarding neurodegenerative diseases.…”

Stilbene Compounds Inhibit Tumor Growth by the Induction of Cellular Senescence and the Inhibition of Telomerase Activity

“…Among the stilbene compounds, trans-resveratrol, also known as 3,4,5,’-tri-hydroxystilbene, and pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene, which is a dimethylether analog of resveratrol), have been well-studied as promising dietary polyphenolic compounds with various chemopreventive and chemotherapeutic effects [134,140]. Previous studies indicated that the regulation of telomerase activity, telomere structure, and telomerase- and telomere-associated binding proteins have been suggested as new avenues for therapeutic intervention for some tumors in which it is difficult to induce apoptosis, such as glioblastoma (GBM) [140]. Mirzazadeh et al indicated that resveratrol (RSV) inhibited hTERT mRNA expression and cell proliferation in U-87 MG cells [140].…”

“…Previous studies indicated that the regulation of telomerase activity, telomere structure, and telomerase- and telomere-associated binding proteins have been suggested as new avenues for therapeutic intervention for some tumors in which it is difficult to induce apoptosis, such as glioblastoma (GBM) [140]. Mirzazadeh et al indicated that resveratrol (RSV) inhibited hTERT mRNA expression and cell proliferation in U-87 MG cells [140]. In a study by Kim et al, the stress hormone norepinephrine (NE) augmented cancer cell proliferation via the β2-adrenergic receptor and induced hTERT activity via Slug, which subsequently increased ovarian cancer cell invasion [143].…”

“…It is now known that cancer is not a single disease, and the idea of a “monoshot” therapeutic strategy is misleading and outdated [140]. Therefore, we propose that the use of stilbene compounds, especially PT, for cancer therapy may be beneficial because PT activity is not limited to the regulation of hTERT activity and expression but is also involved in the downregulation of complex survival pathways in cancer cells.…”