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p53 Protects lung cancer cells against metabolic stress.
Int J Oncol. 2010 Dec; 37(6):1575-81.IJ

Abstract

The preferential use of aerobic glycolysis for energy production by cancer cells, a phenomenon known as the 'Warburg effect', is well recognized and is being considered for therapeutic applications. However, whether inhibition of glycolysis will be effective in all types of cancer is unclear. The current study shows that a glycolytic inhibitor, 2-deoxy-D-glucose (2DG), exhibits the cytotoxic effect on non-small cell lung cancer in a p53-dependent manner. 2DG significantly inhibits ATP production in p53-deficient lung cancer cells (H358) but not in p53-wt cells (A549). In contrast to p53-wt cells, p53-defective cells are unable to compensate for their need of energy via oxidative phosphorylation (OXPHOS) when glycolysis is inhibited. In the presence of p53, increased ROS from OXPHOS increases the expression of p53 target genes known to modulate metabolism, including synthesis of cytochrome c oxidase 2 (SCO2) and TP53-induced glycolysis and apoptosis regulator (TIGAR). Importantly, 2DG selectively induces the expression of the antioxidant enzymes manganese superoxide dismutase (MnSOD) and glutathione peroxidase 1 (GPx1) in a p53-dependent manner. The results demonstrate that the killing of cancer cells by the inhibitor of glycolysis is more efficient in cancer cells without functional p53 and that p53 protects against metabolic stress by up-regulation of oxidative phosphorylation and modulation of antioxidants.

Authors+Show Affiliations

Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21042727

Citation

Sinthupibulyakit, Chompunoot, et al. "P53 Protects Lung Cancer Cells Against Metabolic Stress." International Journal of Oncology, vol. 37, no. 6, 2010, pp. 1575-81.
Sinthupibulyakit C, Ittarat W, St Clair WH, et al. P53 Protects lung cancer cells against metabolic stress. Int J Oncol. 2010;37(6):1575-81.
Sinthupibulyakit, C., Ittarat, W., St Clair, W. H., & St Clair, D. K. (2010). P53 Protects lung cancer cells against metabolic stress. International Journal of Oncology, 37(6), 1575-81.
Sinthupibulyakit C, et al. P53 Protects Lung Cancer Cells Against Metabolic Stress. Int J Oncol. 2010;37(6):1575-81. PubMed PMID: 21042727.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - p53 Protects lung cancer cells against metabolic stress. AU - Sinthupibulyakit,Chompunoot, AU - Ittarat,Wanida, AU - St Clair,William H, AU - St Clair,Daret K, PY - 2010/11/3/entrez PY - 2010/11/3/pubmed PY - 2011/2/25/medline SP - 1575 EP - 81 JF - International journal of oncology JO - Int J Oncol VL - 37 IS - 6 N2 - The preferential use of aerobic glycolysis for energy production by cancer cells, a phenomenon known as the 'Warburg effect', is well recognized and is being considered for therapeutic applications. However, whether inhibition of glycolysis will be effective in all types of cancer is unclear. The current study shows that a glycolytic inhibitor, 2-deoxy-D-glucose (2DG), exhibits the cytotoxic effect on non-small cell lung cancer in a p53-dependent manner. 2DG significantly inhibits ATP production in p53-deficient lung cancer cells (H358) but not in p53-wt cells (A549). In contrast to p53-wt cells, p53-defective cells are unable to compensate for their need of energy via oxidative phosphorylation (OXPHOS) when glycolysis is inhibited. In the presence of p53, increased ROS from OXPHOS increases the expression of p53 target genes known to modulate metabolism, including synthesis of cytochrome c oxidase 2 (SCO2) and TP53-induced glycolysis and apoptosis regulator (TIGAR). Importantly, 2DG selectively induces the expression of the antioxidant enzymes manganese superoxide dismutase (MnSOD) and glutathione peroxidase 1 (GPx1) in a p53-dependent manner. The results demonstrate that the killing of cancer cells by the inhibitor of glycolysis is more efficient in cancer cells without functional p53 and that p53 protects against metabolic stress by up-regulation of oxidative phosphorylation and modulation of antioxidants. SN - 1791-2423 UR - https://www.unboundmedicine.com/medline/citation/21042727/p53_Protects_lung_cancer_cells_against_metabolic_stress_ L2 - http://www.spandidos-publications.com/ijo/37/6/1575 DB - PRIME DP - Unbound Medicine ER -