Zerumbone Promotes Cytotoxicity in Human Malignant Glioblastoma Cells through Reactive Oxygen Species (ROS) Generation
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Mohammad Jalili-Nik1, Mohammad Montazami Sadeghi2, Elmira Mohtashami3
1Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:
Glioblastoma multiforme (GBM) is the most hostile tumor in the central nervous system. Unfortunately, the prognosis of GBM patients is poor following surgical interventions, chemotherapy, and radiotherapy. Consequently, more efficient and effective treatment options for the treatment of GBM need to be explored. Zerumbone, as a sesquiterpene derived from Zingiber zerumbet Smith, has substantial cytotoxic and antiproliferative activities in some types of cancer. Here, we show that exposure of GBM cells (U-87 MG) to Zerumbone demonstrated significant growth inhibition in a concentration-dependent manner. Zerumbone also induced apoptosis and caused cell cycle arrest of human GBM U-87 MG cells in the G2/M phase of the cell cycle. In detail, the apoptotic process triggered by Zerumbone involved the upregulation of proapoptotic Bax and the suppression of antiapoptotic Bcl-2 genes expression as determined by qRT-PCR. Moreover, Zerumbone enhanced the generation of reactive oxygen species (ROS), and N-acetyl cysteine (NAC), as an antioxidant, reversed the ROS-induced cytotoxicity of U-87 MG cells. The Western blot analysis suggested that Zerumbone activated the NF-κB p65, which was partly inhibited by NAC treatment. Collectively, our results confirmed that Zerumbone induces cytotoxicity by ROS generation. Thus, the study raises the possibility of Zerumbone as a potential natural agent for treating GBM due to its ability to induce cytotoxicity.
Insights
Zerumbone, a natural compound, effectively inhibits glioblastoma multiforme (GBM) growth by inducing cell death and halting the cell cycle. This compound generates reactive oxygen species (ROS), offering a potential new avenue for GBM treatment.
Area of Science:
- * Oncology
- * Natural Product Chemistry
- * Molecular Biology
Background:
- * Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor patient prognosis despite standard treatments.
- * There is a critical need for novel and effective therapeutic strategies for GBM.
- * Zerumbone, a sesquiterpene from *Zingiber zerumbet*, exhibits anticancer properties.
Purpose of the Study:
- * To investigate the cytotoxic and antiproliferative effects of Zerumbone on human GBM cells (U-87 MG).
- * To elucidate the mechanisms underlying Zerumbone-induced cell death, including apoptosis, cell cycle arrest, and reactive oxygen species (ROS) generation.
Main Methods:
- * Cell viability assays to assess growth inhibition.
- * Quantitative real-time PCR (qRT-PCR) to analyze gene expression (Bax, Bcl-2).
- * Western blot analysis to detect protein activation (NF-κB p65).
- * Measurement of reactive oxygen species (ROS) generation.
Main Results:
- * Zerumbone significantly inhibited U-87 MG cell growth in a dose-dependent manner.
- * Zerumbone induced apoptosis and G2/M cell cycle arrest in GBM cells.
- * Zerumbone upregulated proapoptotic Bax and downregulated antiapoptotic Bcl-2 expression.
- * Zerumbone increased ROS generation, which was reversed by the antioxidant N-acetyl cysteine (NAC).
- * Zerumbone activated NF-κB p65, an effect partially mitigated by NAC.
Conclusions:
- * Zerumbone exhibits potent cytotoxic and antiproliferative effects against glioblastoma cells.
- * Zerumbone-induced cytotoxicity is mediated, in part, by ROS generation and modulation of apoptosis-related genes.
- * Zerumbone represents a promising natural compound for the development of novel GBM therapies.
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