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

Wang SY, Wei YH, Shieh DB, Lin LL, Cheng SP, Wang PW, Chuang JH - PLoS ONE (2015)

Bottom Line: Doxorubicin and sorafenib are the drugs of choice for treating advanced thyroid cancer but both induce adverse effects.However, dose-dependent reduction in cell viability, intracellular ATP depletion, and extracellular l-lactate production were observed after 2-DG treatment.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Chi-Mei Medical Center, Tainan, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang-Gung University, College of Medicine, Kaohsiung, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus

Susceptibility of PTC cells to 2-DG.(A) Morphological changes were observed using a microscopy (magnification: 200×). BCPAP and CG3 cells were treated for 48 h with 0, 1, 4, and 16 mM 2-deoxy-d-glucose (2-DG). (B) BCPAP and CG3 cells were treated for 48 h with 0, 0.0625, 0.25, 1, and 4 mM 2-DG. Cell viability was measured using a WST-1 assay. Data are shown as a percentage of the controls (untreated) cells. Student’s t test was used to compare the controls and treated cells. *p < 0.05, **p < 0.001, compared to the controls. Data are presented as means ± standard deviation (SD).
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pone.0130959.g002: Susceptibility of PTC cells to 2-DG.(A) Morphological changes were observed using a microscopy (magnification: 200×). BCPAP and CG3 cells were treated for 48 h with 0, 1, 4, and 16 mM 2-deoxy-d-glucose (2-DG). (B) BCPAP and CG3 cells were treated for 48 h with 0, 0.0625, 0.25, 1, and 4 mM 2-DG. Cell viability was measured using a WST-1 assay. Data are shown as a percentage of the controls (untreated) cells. Student’s t test was used to compare the controls and treated cells. *p < 0.05, **p < 0.001, compared to the controls. Data are presented as means ± standard deviation (SD).

Mentions: Given the differences in the bioenergetics of BCPAP and CG3 cells, we compared their responses to different doses of 2-DG, Phase-contrast images showed a decrease in cell number when both cell lines were treated for 48 h with 2-DG alone (1, 4, 16 mM) (Fig 2A). Dose-dependent reductions in cell viability were recorded in BCPAP and in CG3 cells (Fig 2B), without significant differences in the absolute half maximal inhibitory concentration (IC50) of 2-DG-treated cells: 0.32 ± 0.04 mM and 0.30 ± 0.05 mM, respectively (Fig 2B).


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

Wang SY, Wei YH, Shieh DB, Lin LL, Cheng SP, Wang PW, Chuang JH - PLoS ONE (2015)

Susceptibility of PTC cells to 2-DG.(A) Morphological changes were observed using a microscopy (magnification: 200×). BCPAP and CG3 cells were treated for 48 h with 0, 1, 4, and 16 mM 2-deoxy-d-glucose (2-DG). (B) BCPAP and CG3 cells were treated for 48 h with 0, 0.0625, 0.25, 1, and 4 mM 2-DG. Cell viability was measured using a WST-1 assay. Data are shown as a percentage of the controls (untreated) cells. Student’s t test was used to compare the controls and treated cells. *p < 0.05, **p < 0.001, compared to the controls. Data are presented as means ± standard deviation (SD).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4489888&req=5

pone.0130959.g002: Susceptibility of PTC cells to 2-DG.(A) Morphological changes were observed using a microscopy (magnification: 200×). BCPAP and CG3 cells were treated for 48 h with 0, 1, 4, and 16 mM 2-deoxy-d-glucose (2-DG). (B) BCPAP and CG3 cells were treated for 48 h with 0, 0.0625, 0.25, 1, and 4 mM 2-DG. Cell viability was measured using a WST-1 assay. Data are shown as a percentage of the controls (untreated) cells. Student’s t test was used to compare the controls and treated cells. *p < 0.05, **p < 0.001, compared to the controls. Data are presented as means ± standard deviation (SD).
Mentions: Given the differences in the bioenergetics of BCPAP and CG3 cells, we compared their responses to different doses of 2-DG, Phase-contrast images showed a decrease in cell number when both cell lines were treated for 48 h with 2-DG alone (1, 4, 16 mM) (Fig 2A). Dose-dependent reductions in cell viability were recorded in BCPAP and in CG3 cells (Fig 2B), without significant differences in the absolute half maximal inhibitory concentration (IC50) of 2-DG-treated cells: 0.32 ± 0.04 mM and 0.30 ± 0.05 mM, respectively (Fig 2B).

Bottom Line: Doxorubicin and sorafenib are the drugs of choice for treating advanced thyroid cancer but both induce adverse effects.However, dose-dependent reduction in cell viability, intracellular ATP depletion, and extracellular l-lactate production were observed after 2-DG treatment.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Chi-Mei Medical Center, Tainan, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang-Gung University, College of Medicine, Kaohsiung, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus