Amir R. Afshari - Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran|Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
Mostafa Karimi Roshan - 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

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 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.

Brain tumors, Glioblastoma multiforme, Auraptene, Cytotoxicity, Apoptosis