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Published on: December 29, 2017
Effects of telomerase inhibitor on epigenetic chromatin modification enzymes in malignancies
Cigir Biray Avci1, Fatma Dogan1, Neslihan Pinar Ozates Ay1
1Department of Medical Biology, Ege University Medical School, Izmir, Turkey.
Abstract:
Telomerase has a critical role in cell proliferation, tumor maintaining, and therapy resistance, which act by modifying many signaling pathways. 2-[(E)-3-Naphtalen-2-yl-but-2-enoylamino]-benzoic acid (BIBR1532) is one of the most studied telomerase inhibitors, and it targets telomerase components TERC and TERT. In this novel study, we aimed to investigate the epigenetic effects of BIBR1532 on both hematologic malignancies and solid tumors. K-562 human chronic myeloid leukemia cell line and U87MG glioblastoma cell line were compared with control groups without BIBR1532 treatment. Cytotoxic effects of BIBR1532 were determined by using WST-1 assay. Apoptotic effects of BIBR1532 were detected by using annexin V method. To assess expression changes in the human epigenetic chromatin modification enzyme genes, total RNA was isolated from K-562 and U87MG cells treated with BIBR1532 and untreated control cells. BIBR1532 induced 2.41-fold apoptotic cell death in U87MG cell lines compared with control groups. Apoptosis was slightly induced in K-562 cells with BIBR1532 treatment compared with control cells. We observed that BIBR1532 also regulates similar genes in both cell lines, and it is useful on epigenetic mechanisms. As a result, telomerase inhibitor BIBR1532 has a significant effect on both hematological malignancies and solid tumors.
Insights
The telomerase inhibitor BIBR1532 shows significant epigenetic effects in both hematologic malignancies and solid tumors. This compound effectively induced apoptosis in glioblastoma cells and regulated key epigenetic genes in leukemia and glioblastoma cell lines.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Telomerase is crucial for cell proliferation, tumor growth, and therapy resistance.
- Telomerase inhibitors, like BIBR1532, target telomerase components TERC and TERT.
- Understanding the epigenetic impact of telomerase inhibition is vital for cancer therapy.
Purpose of the Study:
- To investigate the epigenetic effects of the telomerase inhibitor BIBR1532.
- To assess BIBR1532's impact on hematologic malignancies and solid tumors.
- To compare epigenetic changes in K-562 (leukemia) and U87MG (glioblastoma) cell lines.
Main Methods:
- Cytotoxicity assessed using WST-1 assay.
- Apoptosis detected via annexin V staining.
- Epigenetic chromatin modification enzyme gene expression analyzed by RNA isolation and sequencing.
Main Results:
- BIBR1532 induced a 2.41-fold increase in apoptosis in U87MG glioblastoma cells.
- Apoptosis was also observed, though to a lesser extent, in K-562 leukemia cells.
- BIBR1532 demonstrated regulation of similar epigenetic genes in both tested cell lines.
Conclusions:
- Telomerase inhibitor BIBR1532 exhibits significant epigenetic effects on both hematologic malignancies and solid tumors.
- BIBR1532's ability to modulate epigenetic mechanisms suggests therapeutic potential.
- The study highlights BIBR1532 as a promising agent for targeting cancer through epigenetic pathways.
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