title: 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.
authors.affiliation: Department of Pediatrics, Chi-Mei Medical Center, Tainan, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang-Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Shuo-Yu
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
authors.forename: Yau-Huei
authors.initials: YH
authors.lastname: Wei
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Dar-Bin
authors.initials: DB
authors.lastname: Shieh
authors.affiliation: Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Department of Surgery, Division of Pediatric Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Lin
authors.affiliation: Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Cheng
authors.affiliation: Department of Internal and Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Wang
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang-Gung University, College of Medicine, Kaohsiung, Taiwan; Department of Surgery, Division of Pediatric Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Jiin-Haur
authors.initials: JH
authors.lastname: Chuang
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D015870:Gene Expression; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009154:Mutation; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010671:Phenylurea Compounds / Q000494:pharmacology*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D000077157:Sorafenib; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D010671:Phenylurea Compounds; D009536:Niacinamide; D019344:Lactic Acid; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D000077157:Sorafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf