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Updated: Jun 10, 2025
A 3D Spheroid Model for Glioblastoma
Published on: April 9, 2020
Vitamin B6 Pathway Maintains Glioblastoma Cell Survival in 3D Spheroid Cultures
Najla Yussuf Moosa1, Sara Abdullah Azeem1, John K Lodge2
1School of Medicine, Murray Health, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland SR1 3SD, UK.
Abstract:
Glioblastoma (GBM) is a deadly brain cancer. The prognosis of GBM patients has marginally improved over the last three decades. The response of GBMs to initial treatment is inevitably followed by relapse. Thus, there is an urgent need to identify and develop new therapeutics to target this cancer and improve both patient outcomes and long-term survival. Metabolic reprogramming is considered one of the hallmarks of cancers. However, cell-based studies fail to accurately recapitulate the in vivo tumour microenvironment that influences metabolic signalling and rewiring. Against this backdrop, we conducted global, untargeted metabolomics analysis of the G7 and R24 GBM 2D monolayers and 3D spheroid cultures under identical cell culture conditions. Our studies revealed that the levels of multiple metabolites associated with the vitamin B6 pathway were significantly altered in 3D spheroids compared to the 2D monolayer cultures. Importantly, we show that pharmacological intervention with hydralazine, a small molecule that reduces vitamin B6 levels, resulted in the cell death of 3D GBM spheroid cultures. Thus, our study shows that inhibition of the vitamin B6 pathway is a novel therapeutic strategy for the development of targeted therapies in GBMs.
Insights
Glioblastoma (GBM) is a deadly brain cancer. Targeting the vitamin B6 pathway with hydralazine shows promise for new GBM therapies by causing cell death in 3D cultures.
Area of Science:
- Oncology
- Cancer Metabolism
- Neuro-oncology
Background:
- Glioblastoma (GBM) remains a lethal brain cancer with limited treatment options.
- Tumor relapse is common after initial GBM treatment, necessitating novel therapeutic strategies.
- Cancer metabolic reprogramming is a key hallmark, but 2D cell cultures do not fully represent the in vivo tumor microenvironment.
Purpose of the Study:
- To investigate metabolic differences between 2D and 3D GBM cultures.
- To identify novel therapeutic targets for glioblastoma.
- To explore the role of the vitamin B6 pathway in GBM.
Main Methods:
- Global, untargeted metabolomics analysis of G7 and R24 GBM cell lines.
- Comparison of 2D monolayer and 3D spheroid GBM cultures.
- Pharmacological intervention using hydralazine to inhibit vitamin B6 levels.
Main Results:
- Significant alterations in vitamin B6 pathway metabolites were observed in 3D GBM spheroids compared to 2D cultures.
- Hydralazine treatment led to cell death in 3D GBM spheroid cultures.
- The vitamin B6 pathway is dysregulated in GBM and represents a potential therapeutic vulnerability.
Conclusions:
- Inhibition of the vitamin B6 pathway is a promising novel therapeutic strategy for glioblastoma.
- Targeting vitamin B6 metabolism could improve patient outcomes and long-term survival in GBM.
- 3D spheroid models are valuable for studying GBM tumor microenvironment and identifying new treatments.
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