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Cytotoxic effects of auraptene against a human malignant glioblastoma cell line.

ABSTRACT: 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 (0-400?g/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-?B, IL-1?, 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 79.17?g/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-?B, IL-1?, 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.

SUBMITTER: Afshari AR

PROVIDER: S-EPMC6612248 | biostudies-literature | 2019 Jul-Aug

REPOSITORIES: biostudies-literature

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Cytotoxic effects of auraptene against a human malignant glioblastoma cell line.

Afshari Amir R AR Karimi Roshan Mostafa M Soukhtanloo Mohammad M Ghorbani Ahmad A Rahmani Farzad F Jalili-Nik Mohammad M Vahedi Mohammad Mahdi MM Hoseini Azar A Sadeghnia Hamid R HR Mollazadeh Hamid H Mousavi Seyed Hadi SH

Avicenna journal of phytomedicine 20190701 4

<h4>Objective</h4>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.<h4>Materials and methods</h4>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 o ...[more]

PMID: 31309072

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Project description:Glioblastoma is a fatal primary malignant brain tumor, and the 5-year survival rate of treated glioblastoma patients still remains <5%. Considering the sustained development of metastasis, tumor recurrence, and drug resistance, there is an urgent need for the novel therapeutic approaches to combat glioblastoma. Trivalent arsenic derivative (arsenite, AsIII) with remarkable clinical efficacy in leukemia has been shown to exert cytocidal effect against glioblastoma cells. Gamabufotalin, an active bufadienolide compound, also shows selective cytocidal effect against glioblastoma cells, and has been suggested to serve as a promising adjuvant therapeutic agent to potentiate therapeutic effect of conventional anticancer drugs. In order to gain novel insight into therapeutic approaches against glioblastoma, the cytotoxicity of AsIII and gamabufotalin was explored in the human glioblastoma cell lines U-87 and U-251. In comparison with U-251 cells, U-87 cells were highly susceptible to the two drugs, alone or in combination. More importantly, clinically achieved concentrations of AsIII combined with gamabufotalin exhibited synergistic cytotoxicity against U-87 cells, whereas showed much less cytotoxicity to human normal peripheral blood mononuclear cells. G2/M cell cycle arrest was induced by each single drug, and further augmented by their combination in U-87 cells. Downregulation of the expression levels of cdc25C, Cyclin B1, cdc2, and survivin was observed in U-87 cells treated with the combined regimen and occurred in parallel with G2/M arrest. Concomitantly, lactate dehydrogenase leakage was also observed. Intriguingly, SB203580, a specific inhibitor of p38 MAPK, intensified the cytotoxicity of the combined regimen in U-87 cells, whereas wortmannin, a potent autophagy inhibitor, significantly rescued the cells. Collectively, G2/M arrest, necrosis and autophagy appeared to cooperatively contribute to the synergistic cytotoxicity of AsIII and gamabufotalin. Given that p38 MAPK serves an essential role in promoting glioblastoma cell survival, developing a possible strategy composed of AsIII, gamabufotalin, and a p38 MAPK inhibitor may provide novel insight into approaches designed to combat glioblastoma.

Dataset Information

Cytotoxic effects of auraptene against a human malignant glioblastoma cell line.

Publications

Cytotoxic effects of auraptene against a human malignant glioblastoma cell line.

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