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Published on: February 9, 2024
Cisplatin downregulates BCL2L12, a novel apoptosis-related gene, in glioblastoma cells
Mahdieh Sadat Taghavi1, Azim Akbarzadeh, Reza Mahdian
1Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. ms.taghavi@srbiau.ac.ir
Abstract:
Glioblastoma progression is mainly characterized by intense apoptosis resistance and marked necrosis. Over-expression of BCL2L12, a novel member of Bcl-2 family has been shown in primary glioblastoma. BCL2L12 blocks effective caspase-3/7 maturation and inhibits p53 tumor suppressor, deriving resistance toward apoptosis and inducing extensive cell necrosis. Cisplatin is a major chemotherapeutic agent which has a broad range of anti-neoplastic activities including apoptosis induction. To investigate the effect of cisplatin on the expression of BCL2L12 in glioblastoma cells, two glioblastoma cell lines were treated with different concentrations of cisplatin for 48 h. The cell viability and IC50 was determined using MTT assay. Then, the two glioblastoma cell lines were treated with 48 h IC50 concentration of cisplatin for 24, 48, and 72 h. Apoptosis induction was analyzed by fluorescence microscopy and flow cytometry. Gene expression study was performed on BCL2L12 and TBP as target and internal control genes, respectively. The quantitative real-time polymerase chain reaction results showed that BCL2L12 gene expression was significantly (p = 0.001) downregulated in the presence of cisplatin. In conclusion, cisplatin treatment induced a time-dependent apoptosis in glioblastoma cells, at least partially via downregulation of BCL2L12 gene expression.
Insights
Cisplatin treatment effectively reduces glioblastoma cell survival by downregulating BCL2L12 gene expression, a key factor in apoptosis resistance. This study demonstrates cisplatin
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Glioblastoma exhibits high apoptosis resistance and necrosis, often linked to BCL2L12 overexpression.
- BCL2L12 inhibits caspase maturation and p53, promoting glioblastoma survival and necrosis.
- Cisplatin is a chemotherapy agent known for inducing apoptosis.
Purpose of the Study:
- To investigate the impact of cisplatin on BCL2L12 gene expression in glioblastoma cells.
- To assess cisplatin's effect on glioblastoma cell viability and apoptosis induction.
- To explore the role of BCL2L12 downregulation in cisplatin's anti-cancer activity.
Main Methods:
- Glioblastoma cell lines were treated with varying cisplatin concentrations.
- Cell viability and IC50 were determined using MTT assay.
- Apoptosis was analyzed via fluorescence microscopy and flow cytometry.
- BCL2L12 gene expression was quantified using quantitative real-time polymerase chain reaction.
Main Results:
- Cisplatin treatment significantly reduced glioblastoma cell viability.
- Quantitative real-time polymerase chain reaction revealed a significant downregulation of BCL2L12 gene expression (p = 0.001) following cisplatin treatment.
- Cisplatin induced time-dependent apoptosis in glioblastoma cells.
Conclusions:
- Cisplatin effectively induces apoptosis in glioblastoma cells.
- The downregulation of BCL2L12 gene expression is a key mechanism by which cisplatin exerts its anti-cancer effects in glioblastoma.
- Cisplatin represents a potential therapeutic strategy for glioblastoma, partly through modulating BCL2L12 levels.
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