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Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
Cytotoxic effects of auraptene against a human malignant glioblastoma cell line
Amir R Afshari1,2, Mostafa Karimi Roshan3, Mohammad Soukhtanloo3
1Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Objective:
Glioblastoma multiforme (GBM) is the deadliest type of primary brain tumors, and the survival of patients is estimated to be only about one year. This study, for the first time, investigated the cytotoxic effects of auraptene on U87 GBM cell line.
Materials And Methods:
The cellular toxicity was measured by the MTT assay following 24 and 48-hr treatment with different concentrations of auraptene (0-400μg/ml). Apoptosis was evaluated by sub-G1 peak in cell cycle analysis of propidium-iodide- stained nuclei. Moreover, to determine the Bax, Bcl-2, MCP-1, NF-κB, IL-1β, and p53 genes expression, we used real-time polymerase chain reaction (RT-PCR).
Results:
The results revealed that auraptene reduced the viability of U87 cells concentration- and time-dependently with IC50 values of 108.9 and 79.17μg/ml obtained for 24 and 48-hr treatments, respectively. Also, sub-G1 population was significantly increased following 24 (p<0.05 and p<0.001) and 48 (p<0.001) hours of treatment. The quantitative real-time RT-PCR showed an up-regulation in Bax, NF-κB, IL-1β, and p53 but a down-regulation in MCP-1 and Bcl-2 genes expression.
Conclusion:
This study showed that auraptene triggered apoptosis probably through Bax/Bcl-2 regulation, blocked cell cycle progression and inhibited proliferation in U87 GBM cells. Taken together, auraptene can be utilized as an effective natural medicine against GBM, after complementary studies.
Insights
Auraptene demonstrates significant cytotoxic effects against U87 glioblastoma cells, inducing apoptosis and inhibiting proliferation. This natural compound shows promise as a potential therapeutic agent for glioblastoma multiforme (GBM).
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with a poor prognosis.
- Limited therapeutic options and a median survival of approximately one year highlight the urgent need for novel treatments.
Purpose of the Study:
- To investigate the cytotoxic effects of auraptene on the U87 GBM cell line.
- To elucidate the molecular mechanisms underlying auraptene's anti-cancer activity in GBM cells.
Main Methods:
- Cell viability was assessed using the MTT assay after 24 and 48-hour treatments with varying auraptene concentrations.
- Apoptosis was evaluated via cell cycle analysis (sub-G1 peak) using propidium iodide staining.
- Gene expression of Bax, Bcl-2, MCP-1, NF-κB, IL-1β, and p53 was quantified using real-time quantitative polymerase chain reaction (RT-PCR).
Main Results:
- Auraptene exhibited concentration- and time-dependent cytotoxicity, with IC50 values of 108.9 μg/ml (24h) and 79.17 μg/ml (48h).
- A significant increase in the sub-G1 apoptotic population was observed after 24 and 48 hours of auraptene treatment.
- RT-PCR analysis revealed differential gene expression, including upregulation of Bax, NF-κB, IL-1β, and p53, and downregulation of MCP-1 and Bcl-2.
Conclusions:
- Auraptene effectively inhibits proliferation and induces apoptosis in U87 GBM cells, likely through modulation of the Bax/Bcl-2 pathway and cell cycle arrest.
- These findings suggest that auraptene holds potential as a natural therapeutic agent for glioblastoma, warranting further investigation.
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