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Published on: March 28, 2021
Juglone in Combination with Temozolomide Shows a Promising Epigenetic Therapeutic Effect on the Glioblastoma Cell
Anna-Maria Barciszewska1,2, Agnieszka Belter3, Iwona Gawrońska3
1Intraoperative Imaging Unit, Chair and Department of Neurosurgery and Neurotraumatology, Karol Marcinkowski University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznan, Poland.
Abstract:
Glioblastoma (GBM) is the most common and aggressive primary brain tumor and one of the human malignancies with the highest mortality. Standard approaches for GBM, including gross total resection, radiotherapy, and chemotherapy, cannot destroy all the cancer cells, and despite advances in its treatment, the prognosis for GBM remains poor. The problem is that we still do not understand what triggers GBM. Until now, the most successful chemotherapy with temozolomide for brain gliomas is not effective, and therefore new therapeutic strategies for GBM are needed. We found that juglone (J), which exhibits cytotoxic, anti-proliferative, and anti-invasive effects on various cells, could be a promising agent for GBM therapy. In this paper, we present the effects of juglone alone and in combination with temozolomide on glioblastoma cells. In addition to the analysis of cell viability and the cell cycle, we looked at the epigenetics effects of these compounds on cancer cells. We showed that juglone induces strong oxidative stress, as identified by a high increase in the amount of 8-oxo-dG, and decreases m5C in the DNA of cancer cells. In combination with TMZ, juglone modulates the level of both marker compounds. Our results strongly suggest that a combination of juglone and temozolomide can be applied for better GBM treatment.
Insights
Juglone shows promise for treating glioblastoma (GBM) by inducing oxidative stress and altering DNA methylation. Combining juglone with temozolomide may offer a new therapeutic strategy for this aggressive brain cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Glioblastoma (GBM) is an aggressive primary brain tumor with poor prognosis despite standard treatments.
- Current therapies, including temozolomide (TMZ), have limited efficacy, necessitating novel therapeutic strategies.
- The underlying triggers of GBM remain poorly understood, highlighting the need for new treatment approaches.
Purpose of the Study:
- To investigate the therapeutic potential of juglone, alone and in combination with temozolomide, against glioblastoma cells.
- To analyze the effects of juglone and temozolomide on glioblastoma cell viability, cell cycle, and epigenetic modifications.
- To explore the impact of these compounds on oxidative stress markers and DNA methylation in cancer cells.
Main Methods:
- Cell viability and cell cycle assays were performed on glioblastoma cells treated with juglone and/or temozolomide.
- Epigenetic effects were assessed by measuring levels of 8-oxo-dG (oxidative damage marker) and m5C (DNA methylation marker).
- Comparative analysis of juglone alone versus juglone in combination with temozolomide was conducted.
Main Results:
- Juglone demonstrated cytotoxic and anti-proliferative effects on glioblastoma cells.
- Juglone significantly increased oxidative stress, indicated by elevated 8-oxo-dG levels.
- Juglone decreased DNA methylation (m5C) in cancer cells, and this effect was modulated when combined with temozolomide.
Conclusions:
- Juglone exhibits promising anti-cancer properties against glioblastoma through oxidative stress induction and epigenetic modulation.
- The combination of juglone and temozolomide may represent a more effective therapeutic strategy for glioblastoma treatment.
- Further research into juglone's mechanisms and its synergistic effects with chemotherapy is warranted for improved GBM therapy.
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