• Mustafa Aziz Hatiboglu, Abdurrahim Kocyigit, Eray Metin Guler, Kerime Akdur, Arife Nalli, Ersin Karatas, and Saffet Tuzgen.
• Department of Neurosurgery, Bezmialem Vakif University Medical School, Istanbul, Turkey. Electronic address: mhatiboglu@bezmialem.edu.tr.
• World Neurosurg. 2018 Jun 1; 114: e182-e190.

BackgroundPrognosis of patients with melanoma brain metastasis is poor despite various chemotherapeutic agents. Researchers focus on finding effective treatment with a low risk of toxicity. Thymoquinone (TQ) has been found to be effective on different types of cancer. However, no data exist regarding the effect of TQ in intracerebral melanoma. The purpose of this study was to assess the effect of TQ in B16-F10 melanoma cell in vitro and intracerebral melanoma in vivo.MethodsThe mechanisms of efficacy were investigated using adenosine triphosphate assay for cytotoxicity, flow cytometry, and acridine orange staining for apoptosis, comet assay for genotoxicity, CM-H2DCF-DA (2,7-dichlorodihydrofluorescein) for intracellular reactive oxygen species (ROS) generation and ELISA methods for inflammatory cytokines. Western blotting was performed to assess the expressions of p-JAK2, p-STAT3, caspase-3, Bax, Bcl-2, and survivin. In addition, the effect of TQ was investigated in a model system of intracerebral melanoma in syngeneic mice.ResultsThe median survival was improved by TQ in mice with intracerebral melanoma compared with the control group (16 days vs 9 days; P = 0.008). Cytotoxicity was enhanced by TQ in B16-F10 cells in a dose-dependent manner. TQ also induced apoptosis, DNA damage, and increased intracellular ROS. TQ inhibited p-STAT3, resulting in apoptosis through regulation of proapoptotic and antiapoptotic proteins.ConclusionsOur findings suggest that TQ would be an effective treatment in intracerebral metastatic lesions. This warrants further investigation.Copyright © 2018 Elsevier Inc. All rights reserved.

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