Auraptene-induced cytotoxicity mechanisms in human malignant glioblastoma (U87) cells: role of reactive oxygen species (ROS)

Authors

  • Amir R. Afshari Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran; Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Mohammad Jalili-Nik Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Mohammad Soukhtanloo Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Ahmad Ghorbani Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
  • Hamid R. Sadeghnia Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Hamid Mollazadeh Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
  • Mostafa Karimi Roshan Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Farzad Rahmani Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Hamed Sabri Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Mohammad Mahdi Vahedi Department of Pharmacology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran; Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
  • Seyed Hadi Mousavi Medical Toxicology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 917794-8564, Iran. E-mail: Mousavih@mums.ac.ir

DOI:

https://doi.org/10.17179/excli2019-1136

Keywords:

glioblastoma multiforme, auraptene, ROS, apoptosis

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 effects 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.

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Published

2019-07-30

How to Cite

Afshari, A. R., Jalili-Nik, M., Soukhtanloo, M., Ghorbani, A., Sadeghnia, H. R., Mollazadeh, H., … Mousavi, S. H. (2019). Auraptene-induced cytotoxicity mechanisms in human malignant glioblastoma (U87) cells: role of reactive oxygen species (ROS). EXCLI Journal, 18, 576–590. https://doi.org/10.17179/excli2019-1136

Issue

Vol. 18 (2019)

Section

Original articles

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