Authors: Afshari, Amir R.
Jalili-Nik, Mohammad
Soukhtanloo, Mohammad
Ghorbani, Ahmad
Sadeghnia, Hamid R.
Mollazadeh, Hamid
Karimi Roshan, Mostafa
Rahmani, Farzad
Sabri, Hamed
Vahedi, Mohammad Mahdi
Mousavi, Seyed Hadi
Title: Auraptene-induced cytotoxicity mechanisms in human malignant glioblastoma (U87) cells
Other Titles: role of reactive oxygen species (ROS)
Language (ISO): en
Abstract: Glioblastoma multiforme (GBM), like the devastating type of astrocytic tumors, is one of the most challenging cancers to treat owing to its aggressive nature. Auraptene, as a prenyloxy coumarin from citrus species, represents antioxidant and antitumor activities; however, the underlying antitumor mechanisms of auraptene against GBM remain unclear. The present study aimed to evaluate the cytotoxic and apoptogenic effect s of auraptene, as a promising natural product, and the possible signaling pathways affected in human malignant GBM (U87) cells. Reactive oxygen species (ROS) production significantly decreased in the first 2, and 6 hours after treatment with auraptene however, ROS levels increased in other incubation times (8 and 24 hours), dramatically. N-acetyl-cysteine (NAC) markedly attenuated auraptene–induced ROS production, and consequently reversed auraptene–induced cytotoxicity in 8 and 24 hours after treatment, as well. Induction of apoptosis occurred in the first 24- and 48-hours concentration-dependently. The qRT-PCR showed an up-regulation in p21, CXCL3, and a down-regulation in Cyclin D1 genes expression. Western blot analysis confirmed the up-regulation of the Bax/Bcl-2 ratio protein levels concentration-dependently. Hence, this study collectively revealed that the increase in ROS level is at least one of the mechanisms associated with auraptene-induced GBM cell toxicity as well as the induction of apoptosis through Bax/Bcl-2 modulation and genes expression involved that contribute to the cytotoxicity of auraptene in U87 cells. So, auraptene might be utilized as a potential novel anti-GBM agent after further studies.
Subject Headings: Glioblastoma multiforme
Auraptene
ROS
Apoptosis
URI: http://hdl.handle.net/2003/39016
http://dx.doi.org/10.17877/DE290R-20935
Issue Date: 2019-07-30
Rights link: https://creativecommons.org/licenses/by/4.0/
Appears in Collections:Original Articles

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