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Temozolomide may induce cell cycle arrest by interacting with URG4/URGCP in SH-SY5Y neuroblastoma cells
Veli Çıtışlı1, Yavuz Dodurga2, Canan Eroğlu3
1Department of Neurosurgery, Pamukkale University School of Medicine, Denizli, Turkey.
Abstract:
Temozolomide (TMZ) is an alkylating drug used usually in glioma treatment by inducing the apoptosis in glioma cell. The aim of the study is to investigate the anticancer mechanism of TMZ in SH-SY5Y human neuroblastoma cell line. Cytotoxic effects of TMZ were determined by using XTT assay. IC50 doses in the SH-SY5Y were detected as 5 mM. Expression profiles of novel genes URG4/URGCP, CCND1, CCND2, CDK4, and BCL2 were determined by real-time PCR. The apoptotic effects of TMZ were evaluated with TUNEL method. Furthermore, effects of TMZ on colony formation and invasion were investigated in this study. It was observed that TMZ in SH-SY5Y cell line caused a significant decrease in the gene expressions of URG4/URGCP, CCND1, CCND2, CDK4, and BCL2. According to TUNEL assay results, TMZ markedly induced apoptosis in SH-SY5Y cell line. It was found that TMZ in SH-SY5Y cell line suppressed invasion and colony formation using matrigel invasion chamber and colony formation assay, respectively. To conclude, it is thought that TMZ demonstrates anticarcinogenesis activity by affecting cell cycle arrest, apoptosis, invasion, and colony formation on SH-SY5Y cells. TMZ may be an effective agent for treatment of neuroblastoma as a single or in combination with other drugs.
Insights
Temozolomide (TMZ) effectively combats neuroblastoma cells by inducing apoptosis and inhibiting cell cycle progression, invasion, and colony formation. This alkylating drug shows promise as a single agent or in combination therapy for neuroblastoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Temozolomide (TMZ) is an alkylating agent commonly used in glioma treatment.
- TMZ functions by inducing apoptosis in cancer cells.
Purpose of the Study:
- To investigate the anticancer mechanisms of TMZ in the SH-SY5Y human neuroblastoma cell line.
- To evaluate the effects of TMZ on gene expression, apoptosis, cell cycle, invasion, and colony formation.
Main Methods:
- XTT assay for cytotoxicity and IC50 determination.
- Real-time PCR for gene expression analysis (URG4/URGCP, CCND1, CCND2, CDK4, BCL2).
- TUNEL assay for apoptosis, Matrigel invasion chamber assay for invasion, and colony formation assay.
Main Results:
- TMZ exhibited cytotoxic effects with an IC50 of 5 mM in SH-SY5Y cells.
- TMZ significantly decreased the expression of URG4/URGCP, CCND1, CCND2, CDK4, and BCL2.
- TMZ markedly induced apoptosis and suppressed invasion and colony formation in SH-SY5Y cells.
Conclusions:
- TMZ demonstrates anticarcinogenesis activity in neuroblastoma cells by impacting cell cycle arrest, apoptosis, invasion, and colony formation.
- TMZ holds potential as an effective therapeutic agent for neuroblastoma, either alone or in combination therapies.
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