Glut-1 antibodies induce growth arrest and apoptosis in human cancer cell lines

Rastogi, Shipra; Banerjee, Soumya; Chellappan, Srikumar; Simon, George R.

doi:10.1016/j.canlet.2007.07.021

Cited by 101 publications

(79 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glucose transporter-1 (GLUT-1) is a member of the GLUT family, which is expressed in erythrocytes, endothelial cells, placenta and blood-tissue barriers, including the blood-brain and blood-nerve barriers (10,11). Recent studies have demonstrated that GLUT-1 is often upregulated in various malignant tumors, including colorectal cancer (12), esophageal cancer (13), oral squamous cell carcinoma (14), renal cell carcinoma (15) breast cancer and lung cancer (16). It is also considered to be the predominantly elevated glucose transporter under ischemic and hypoxic conditions, whereby cells require glycolysis as an energy source.…”

Section: Introductionmentioning

confidence: 99%

Expression and clinical significance of glucose transporter-1 in pancreatic cancer

Lǚ

Yang

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract.Increasing evidence has demonstrated that malignant cells exhibit increased glucose uptake, which facilitates survival and growth in a hypoxic environment. The glucose transporter-1 (GLUT-1) is overexpressed in a variety of malignant tumors. However, the association between GLUT-1 expression and clinicopathological factors, 18 F-fluorodeoxyglucose uptake and tumor proliferation in pancreatic cancer has not been investigated to date. In the present study, the expression of GLUT-1 in 53 pancreatic cancer tissues was analyzed, which revealed that GLUT-1 was overexpressed in pancreatic tissue and correlated with poor prognosis and clinicopathological characteristics, including increased tumor size, clinical stage and lymph node metastasis, maximum standardized uptake value (SUV max ) and Ki-67 expression. The receiver operating characteristic curve analysis indicated that a cut-off SUV max value of 4.830 was associated with optimal sensitivity (88%) and specificity (71.4%) for the detection of strong positive GLUT-1 expression. In addition, as the expression of GLUT-1 was found to correlate with Ki-67 expression, GLUT-1 may exhibit a significant effect on cell proliferation in pancreatic cancer. Overall, these findings indicate that GLUT-1 may represent a prognostic indicator, and a potential therapeutic target for pancreatic cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Expression and clinical significance of glucose transporter-1 in pancreatic cancer

Lǚ

Yang

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…Glut1 has not been targeted until very recently due to the lack of potent and selective inhibitors. First, Glut1 antibodies were shown to inhibit cancer cell growth (15). Other Glut1 inhibitors and glucose transport inhibitors, such as fasentin (16) and phloretin (17), were also shown to be effective in reducing cancer cell growth.…”

Section: Introductionmentioning

confidence: 99%

A Small-Molecule Inhibitor of Glucose Transporter 1 Downregulates Glycolysis, Induces Cell-Cycle Arrest, and Inhibits Cancer Cell Growth In Vitro and In Vivo

Liu

Cao

Zhang

et al. 2012

Molecular Cancer Therapeutics

457

389

View full text Add to dashboard Cite

The functional and therapeutic importance of the Warburg effect is increasingly recognized, and glycolysis has become a target of anticancer strategies. We recently reported the identification of a group of novel small compounds that inhibit basal glucose transport and reduce cancer cell growth by a glucose deprivation-like mechanism. We hypothesized that the compounds target Glut1 and are efficacious in vivo as anticancer agents. Here, we report that a novel representative compound WZB117 not only inhibited cell growth in cancer cell lines but also inhibited cancer growth in a nude mouse model. Daily intraperitoneal injection of WZB117 at 10 mg/kg resulted in a more than 70% reduction in the size of human lung cancer of A549 cell origin. Mechanism studies showed that WZB117 inhibited glucose transport in human red blood cells (RBC), which express Glut1 as their sole glucose transporter. Cancer cell treatment with WZB117 led to decreases in levels of Glut1 protein, intracellular ATP, and glycolytic enzymes. All these changes were followed by increase in ATPsensing enzyme AMP-activated protein kinase (AMPK) and declines in cyclin E2 as well as phosphorylated retinoblastoma, resulting in cell-cycle arrest, senescence, and necrosis. Addition of extracellular ATP rescued compound-treated cancer cells, suggesting that the reduction of intracellular ATP plays an important role in the anticancer mechanism of the molecule. Senescence induction and the essential role of ATP were reported for the first time in Glut1 inhibitor-treated cancer cells. Thus, WZB117 is a prototype for further development of anticancer therapeutics targeting Glut1-mediated glucose transport and glucose metabolism.

show abstract

“…24 Moreover, antibodies to Glut-1 decrease proliferation and induce apoptosis in breast cancer cell lines by decreasing glucose uptake. 25 The uptake of the two glucose analogues, deoxyd-glucose (DG) and 3-O-methylglucose (OMG) correlated with proliferative index in the tumor cell line SW620. 26 Increased glucose uptake by tumor cells is exploited in cancer imaging using the positron-labeled glucose analogue 18F-FDG, which is transported into cells but undergoes little further metabolism.…”

Section: Resultsmentioning

confidence: 99%