The in vitro effect of the diabetes-associated markers insulin, leptin and oxidative stress on cellular characteristics promoting breast cancer progression is GLUT1-dependent

The pro‐proliferative effect of insulin in human breast epithelial DMBA‐transformed and non‐transformed cell lines is PI3K‐, mTOR‐ and GLUT1‐dependent

“…35 This effect of insulin agrees with a previous in vitro study from our group showing that high insulin concentrations promote cell proliferation and VEGF-A production in both ER-positive and triple-negative breast cancer cell lines. 8 So, insulin appears to stimulate angiogenesis associated with both cancer initiation and progression. Additionally, cell cycle analysis showed that insulin caused a slight but significant decrease in the G2/M phase population of nontumoural cells, while promoting a decrease in the G1 phase cell cycle population accompanied by a significant increase in the number of cells occupying the S phase in DMBA-transformed cells.…”

“…8 BAY-876 is a recently promising compound identified as a new-generation selective inhibitor of GLUT1. 34 GLUT1 constitutes a principal mechanism for the increased proliferation and malignant potential of breast cancer cells, 8,12,13 and its overexpression appears especially important for the initiation of breast tumorigenesis, 14 as well as to maintain tumour growth. 12 We thus decided to investigate if the stimulatory effect of insulin upon cell proliferation and 3 H-DG uptake is sensitive to BAY-876.…”

“…DNA synthesis rates were evaluated by quantification of incorporation of 3 H-thymidine (μCi/mg total protein), as described. 8,24 Intracellular radioactivity was measured by liquid scintillation counting (LKB Wallac 1209 Rackbeta, Turku, Finland). Results were normalized for total protein content (Bradford method).…”

“…Cell migration rates were determined by a scratch injury assay, as described. 8,24 Images were obtained at 0 and 24 hours after the scratch, and quantification was performed using the ImageJ software (NIH, Bethesda, Maryland).…”

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

“…Over-expression of GLUT1 has been identified during tumorigenesis and progression in several kinds of human malignancies, and is regulated by hypoxia, steroid hormones, growth hormones, insulin, and some oncogenes (13)(14)(15). At present, there have been few reports investigating GLUT1 inhibitors (16)(17)(18)(19)(20). Among these, the most specific, most representative and effective is BAY-876, which is water-insoluble yellow powder (21).…”