2-Deoxy-d-Glucose Can Complement Doxorubicin and Sorafenib to Suppress the Growth of Papillary Thyroid Carcinoma Cells

Abstract

Tumor cells display a shift in energy metabolism from oxidative phosphorylation to aerobic glycolysis. A subset of papillary thyroid carcinoma (PTC) is refractory to surgery and radioactive iodine ablation. Doxorubicin and sorafenib are the drugs of choice for treating advanced thyroid cancer but both induce adverse effects. In this study, we assessed the anti-cancer activity of 2-deoxy-d-glucose (2-DG) alone and in combination with doxorubicin or sorafenib in PTC cell lines with (BCPAP) and without (CG3) the BRAFV600E mutation. BCPAP cells were more glycolytic than CG3 cells, as evidenced by their higher extracellular l-lactate production, lower intracellular ATP level, lower oxygen consumption rate (OCR), and lower ratio of OCR/extracellular acidification rate. However, dose-dependent reduction in cell viability, intracellular ATP depletion, and extracellular l-lactate production were observed after 2-DG treatment. Regression analysis showed that cell growth in both cell lines was dependent on ATP generation. 2-DG increased the chemosensitivity of BCPAP and CG3 cell lines to doxorubicin and sorafenib. These results demonstrate that the therapeutic effects of low combined doses of 2-DG and doxorubicin or sorafenib are similar to those of high doses of doxorubicin or sorafenib alone in PTC cell lines regardless of the BRAFV600E mutation.

Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells

“…Apoptosis detection. Briefly, the cells were treated with caulerpin for 24 h. Cells (1x10 6 ) were centrifuged and harvested (18). Next, the cells were suspended in binding buffer, containing Annexin V-FITC and PI and then incubated for 15 min in the dark at room temperature.…”

Combined Treatment with 2-Deoxy-D-Glucose and Doxorubicin Enhances the in Vitro Efficiency of Breast Cancer Radiotherapy

“…Glucose analogs have been found to profoundly inhibit glucose metabolism in cancer cells in vitro and in vivo (Gupta et al, 2009;Sinthupibulyakit et al, 2009;Zhang and Aft, 2009;Ahmad et al, 2010;Mustafa et al, 2015). Of the many glucose analogs which have been investigated, 2-Deoxy-D-Glucose (2DG) has been proven effective in the inhibition of tumor metabolism and ATP production (Gupta et al, 2009;Ahmad et al, 2010;Mustafa et al, 2015;Wang et al, 2015). Therefore, 2DG has suggested as an adjuvant of radiation therapy and chemotherapy both in vitro and in vivo (Gupta et al, 2009).…”

Near-simultaneous quantification of glucose uptake, mitochondrial membrane potential, and vascular parameters in murine flank tumors using quantitative diffuse reflectance and fluorescence spectroscopy

“…Taken together, glycolysis, mitochondrial oxidative phosphorylation, and vascular parameters all play a key role in understanding how the metabolic characteristics of tumors impact therapeutic outcome, and the ability to monitor all of them simultaneously can play an important role in cancer pharmacology research. A common tool for assessing glycolysis and oxidative phosphorylation is the ubiquitous Seahorse Assay, which treats cells in vitro with chemical perturbations to measure two functional endpoints: oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) [8][9][10][11][12][13]. The Seahorse instrument is widely used for biomedical research as evidenced by over 500 journal articles in 2017 alone [14].…”

“…However, metabolomics is mainly used for ex vivo tissue samples and only provides a snapshot of the tissue's metabolic state. By using 13 C labeled glucose or other metabolites, it is possible to acquire metabolic fluxes [23]. However, this requires highly sophisticated technology and software for such analyses.…”

“…18 FFMISO) [30], however, both glucose uptake and hypoxia cannot be measured simultaneously. Magnetic resonance spectral imaging (MR(S)I) can report on mitochondrial metabolism and glycolysis using special tracers such as 31 P or hyperpolarized 13 C labeled compounds [31,32]. Additionally, vascular imaging can be accomplished with a range of magnetic resonance imaging (MRI) techniques [33,34], including blood oxygen level dependent (BOLD) MRI [33,35], dynamic contrastenhanced (DCE) MRI [30,36], and dynamic susceptibility contrast (DSC) MRI [37].…”