Dietary 2-deoxy-D-glucose impairs tumour growth and metastasis by inhibiting angiogenesis
Saurabh Singh1, Sanjay Pandey1, Amanpreet Singh Chawla2
1Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India; Medical Biotechnology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India; Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY, USA.
Abstract:
Accumulating evidence suggests the antiangiogenic potential of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) among the anticancerous properties of this drug. In the present studies, we investigated the antiangiogenic effects of dietary 2-DG on tumour (Lewis lung carcinoma [LLC]) as well as ionising radiation-induced angiogenesis in mouse models. Dietary 2-DG reduced the serum vascular endothelial growth factor levels (∼40%) in LLC-bearing mice along with a significant inhibition of tumour growth and metastases. In vivo Matrigel plug assays showed significant decrease in vascularisation, Fluorescein isothiocyanate (FITC)-dextran fluorescence and factor VIII-positive cells in the plugs from 2-DG-fed mice, supporting the notion that dietary 2-DG significantly suppresses the tumour-associated and radiation-induced angiogenesis. 2-DG inhibited the glucose usage and lactate production as well as ATP levels of human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner, accompanied by growth inhibition and loss of viability in vitro. Furthermore, 2-DG inhibited the capillary-like tube formation in Matrigel as well as migration and transwell invasion by HUVECs, which are functional indicators of the process of angiogenesis. These results suggest that dietary 2-DG inhibits processes related to angiogenesis, which can impair the growth and metastasis of tumours.
Insights
Dietary 2-deoxy-D-glucose (2-DG) inhibits angiogenesis, suppressing tumor growth and metastasis. This glycolytic inhibitor reduces vascularization and endothelial cell function, offering potential in cancer therapy.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- The glycolytic inhibitor 2-deoxy-D-glucose (2-DG) exhibits anticancer properties.
- Evidence suggests 2-DG possesses antiangiogenic potential, crucial for tumor growth and metastasis.
Purpose of the Study:
- To investigate the antiangiogenic effects of dietary 2-DG.
- To evaluate 2-DG's impact on tumor-associated and radiation-induced angiogenesis in mouse models.
Main Methods:
- Dietary administration of 2-DG to mice bearing Lewis lung carcinoma (LLC) and exposed to ionizing radiation.
- In vivo Matrigel plug assays to assess vascularization.
- In vitro studies using human umbilical vein endothelial cells (HUVECs) to evaluate glucose metabolism, ATP levels, and angiogenic functions.
Main Results:
- Dietary 2-DG significantly reduced serum vascular endothelial growth factor (VEGF) levels by approximately 40% in LLC-bearing mice.
- Tumor growth and metastasis were significantly inhibited in mice fed with 2-DG.
- In vivo and in vitro assays demonstrated suppressed vascularization, reduced endothelial cell viability, and inhibited capillary-like tube formation, migration, and invasion.
Conclusions:
- Dietary 2-DG effectively suppresses tumor-associated and radiation-induced angiogenesis.
- 2-DG inhibits key cellular processes involved in angiogenesis, including glucose metabolism and endothelial cell function.
- These findings suggest that 2-DG has therapeutic potential in impairing tumor growth and metastasis through its antiangiogenic effects.
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