Document Type : Original Research Article
Authors
1
Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2
Department of Pharmacology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
3
Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
4
Department of Biology, School of Computer, Mathematical, and Natural Sciences, Morgan State University, Baltimore, MD 21251, USA
5
Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
10.22038/ajp.2026.89447.4144
Abstract
Objective: Glioblastoma (GB) poses a significant clinical challenge due to its aggressive nature and resistance to temozolomide (TMZ). This study investigated the natural compound tschimgin, alone and in combination with TMZ, as a potential therapeutic strategy against TMZ-resistant GB cells.
Materials and methods: The study assessed the effects of tschimgin and TMZ, alone and combined, on TMZ-resistant glioblastoma cells (T98G) and normal fibroblasts (HFF) using MTT assays, combination index analysis, cell cycle analysis, reactive oxygen species (ROS) measurements, caspase activity tests, and qRT-PCR for Bax/Bcl-2 expression.
Results: Tschimgin significantly enhanced TMZ-induced cytotoxicity in T98G cells, with minimal impact on HFF cells. The combined treatment resulted in a substantial reduction in cell survival compared to either treatment alone. Moreover, findings revealed that both compounds, particularly in combination, induced cell cycle arrest at the sub-G1 and G2/M phases, increased ROS production, increased caspase 3/7 activity, and upregulated the Bax/Bcl2 ratio. The increase in the Bax/Bcl-2 ratio was driven primarily by significant upregulation of Bax, while Bcl-2 levels remained largely unchanged.
Conclusion: The combination of tschimgin and TMZ exhibits a synergistic effect on TMZ-resistant GB cells, suggesting it as a potential therapeutic strategy for patients with resistant tumors. These findings suggest that tschimgin may serve as an adjunct therapeutic agent to enhance the efficacy of TMZ in resistant GB. However, further mechanistic, in vivo, and clinical studies are warranted to evaluate the effectiveness and safety of this compound.
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