TY - JOUR
T1 - Dietary 2-deoxy-D-glucose impairs tumour growth and metastasis by inhibiting angiogenesis
AU - Singh, Saurabh
AU - Pandey, Sanjay
AU - Chawla, Amanpreet Singh
AU - Bhatt, Anant Narayan
AU - Roy, Bal Gangadhar
AU - Saluja, Daman
AU - Dwarakanath, Bilikere S.
N1 - Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
KW - 2-Deoxy-D-glucose
KW - Energy restriction
KW - Lewis lung carcinoma
KW - Radiation-induced angiogenesis
KW - Tumour-induced angiogenesis
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U2 - 10.1016/j.ejca.2019.09.005
DO - 10.1016/j.ejca.2019.09.005
M3 - Article
C2 - 31670076
AN - SCOPUS:85073758228
SN - 0959-8049
VL - 123
SP - 11
EP - 24
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -