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A comparative analysis of inhibitors of the glycolysis pathway in breast and ovarian cancer cell line models
A comparative analysis of inhibitors of the glycolysis pathway in breast and ovarian cancer cell line models
- Source :
- Oncotarget, Xintaropoulou, C, Ward, C, Wise, A, Marston, H, Turnbull, A & Langdon, S 2015, ' A comparative analysis of inhibitors of the glycolysis pathway in breast and ovarian cancer cell line models ', Oncotarget . https://doi.org/10.18632/oncotarget.4499
- Publication Year :
- 2015
-
Abstract
- Many cancer cells rely on aerobic glycolysis for energy production and targeting of this pathway is a potential strategy to inhibit cancer cell growth. In this study, inhibition of five glycolysis pathway molecules (GLUT1, HKII, PFKFB3, PDHK1 and LDH) using 9 inhibitors (Phloretin, Quercetin, STF31, WZB117, 3PO, 3-bromopyruvate, Dichloroacetate, Oxamic acid, NHI-1) was investigated in panels of breast and ovarian cancer cell line models. All compounds tested blocked glycolysis as indicated by increased extracellular glucose and decreased lactate production and also increased apoptosis. Sensitivity to several inhibitors correlated with the proliferation rate of the cell lines. Seven compounds had IC50 values that were associated with each other consistent with a shared mechanism of action. A synergistic interaction was revealed between STF31 and Oxamic acid when combined with the antidiabetic drug metformin. Sensitivity to glycolysis inhibition was also examined under a range of O2 levels (21% O2, 7% O2, 2% O2 and 0.5% O2) and greater resistance to the inhibitors was found at low oxygen conditions (7% O2, 2% O2 and 0.5% O2) relative to 21% O2 conditions. These results indicate growth of breast and ovarian cancer cell lines is dependent on all the targets examined in the glycolytic pathway with increased sensitivity to the inhibitors under normoxic conditions.
- Subjects :
- Phloretin
Antineoplastic Agents
Apoptosis
Breast Neoplasms
Pharmacology
Biology
chemistry.chemical_compound
Glycolysis Inhibition
Inhibitory Concentration 50
breast cancer
inhibitors
medicine
Humans
Glycolysis
Lactic Acid
Molecular Targeted Therapy
Cell Proliferation
Ovarian Neoplasms
Dose-Response Relationship, Drug
Cell growth
Drug Synergism
glycolysis
medicine.disease
Cell Hypoxia
Oxygen
Glucose
ovarian cancer
Oncology
chemistry
Anaerobic glycolysis
Cancer cell
MCF-7 Cells
Female
Ovarian cancer
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 6
- Issue :
- 28
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....1446f6ebdc5a974e8c703424abb0da66
- Full Text :
- https://doi.org/10.18632/oncotarget.4499