Glucose Metabolism in Cancer and Ischemia: Possible Therapeutic Consequences of the Warburg Effect.

Spela Salamon, Eva Podbregar, Peter Kubatka, Dietrich Büsselberg, Martin Caprnda, Radka Opatrilova, Vanda Valentova, Mariusz Adamek, Peter Kruzliak, Matej Podbregar

Journal: Nutrition and cancer 2018;69(2):177-183

PMID: 28094552

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Abstract

The Warburg effect states that the main source of energy for cancer cells is not aerobic respiration, but glycolysis-even in normoxia. The shift from one to the other is governed by mutually counteracting enzymes: pyruvate dehydrogenase and pyruvate dehydrogenase kinase (PDK). Anaerobic metabolism of cancer cells promotes cell proliferation, local tissue immunosuppression, resistance to hypoxic conditions, and metastatic processes. By switching glucose back to oxidative metabolism, these effects might be reversed. This can be achieved using PDK inhibitors, such as dichloroacetate. Patients suffering from ischemic conditions might benefit from this effect. On the other hand, the β-blockers (adrenergic β-antagonists) often used in these patients appear to improve cancer-specific survival, and nonselective β-blockers have been shown to promote glucose oxidation. Might there be a link?

Address: a Medical Faculty, University of Maribor , Maribor , Slovenia.; b Medical Faculty, University of Ljubljana , Ljubljana , Slovenia.; c Department of Medical Biology , Jessenius Faculty of Medicine, Comenius University in Bratislava , Martin , Slovakia.; d Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava , Martin , Slovakia.; e Weill Cornell Medicine in Qatar , Qatar Foundation-Education City , Doha , Qatar.; f 2nd Department of Internal Medicine , Faculty of Medicine, Comenius University and University Hospital , Bratislava , Slovakia.; g Department of Chemical Drugs , Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences , Brno , Czech Republic.; c Department of Medical Biology , Jessenius Faculty of Medicine, Comenius University in Bratislava , Martin , Slovakia.; h Department of Thoracic Surgery , Faculty of Medicine and Dentistry, Medical University of Silesia , Katowice , Poland.; g Department of Chemical Drugs , Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences , Brno , Czech Republic.; i Department of Medical Physics and Biophysics , Faculty of Medicine, Pavol Jozef Safarik University , Kosice , Slovakia.; j 2nd Department of Surgery , Faculty of Medicine, St. Anne's University Hospital and Masaryk University , Brno , Czech Republic.; k Clinical Department for Anesthesiology and Intensive Care , University Medical Center Ljubljana , Slovenia.

DOI: 10.1080/01635581.2017.1263751

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MeSH Terms: Adrenergic beta-Antagonists, Dichloroacetic Acid, Glucose, Glycolysis, Humans, Ischemia, Neoplasms