WARBURG HYPOTHESIS

The 'Warburg's hypothesis' was postulated by the scientist Otto Heinrich Warburg in 1924. He hypothesized that cancer, maligant growth, and tumor growth are caused by the fact that tumor cells mainly generate energy (as e.g. adenosine triphosphate / ATP) by non-oxidative breakdown of glucose (a process called glycolysis). This is in contrast to "healthy" cells which mainly generate energy from oxidative breakdown of pyruvate. Pyruvate is an end-product of glycolysis, and is oxidized within the mitochondria. Hence and according to Warburg, cancer should be interpreted as a mitochondrial dysfunction. Warburg reported a fundamental difference between normal and cancerous cells to be the ratio of glycolysis to respiration.
It is now known that cancer is caused by mutations in the genome of the cells in a process called malignant transformation, resulting in an uncontrolled growth of cells. The metabolic differences observed by Warburg are an adaption of cancer cells to the hypoxic (oxygen-deficient) conditions inside solid tumors, but are not the cause of cancer.
Warburg articulated this hypothesis in a paper entitled ''The Prime Cause and Prevention of Cancer'' which he presented in lecture at the meeting of the Nobel-Laureates on June 30, 1966 at Lindau, Lake Constance, Germany. In this speech, Warburg presented evidence in support of the claim that anaerobiosis was a primary cause of cancerous cells. Put in his own words, "the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar."^[1]
In recent years, Warburg's hypothesis has re-gained attention due to several discoveries linking impaired mitochondrial function as well as impaired respiration to growth, division and expansion of tumor cells. In a study by Michael Ristow and co-workers, colon cancer lines were modified to overexpress frataxin. The results of their work suggest that an increase in oxidative metabolism induced by mitochondrion frataxin may inhibit cancer growth in mammals.^[2]
Subsequent work has shown that this observation, indeed, might be a promising approach in the treatment of solid tumors.^[3][4]
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Contents

See also

References

Further reading

See also

★ Carcinogen

★ Pyruvic acid

References

(i) first German publication (article) --- O. Warburg, K. Posener, E. Negelein: Ueber den Stoffwechsel der Tumoren; Biochemische Zeitschrift, Vol. 152, pp. 319-344, 1924.
(ii) first set of reprints in English (book) --- O. Warburg, On metabolism of tumors, Publisher: Constable, London, 1930.
1.
2. Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth: Otto Warburg revisited., Schulz TJ, Thierbach R, Voigt A, Drewes G, Mietzner B, Steinberg P, Pfeiffer AF, Ristow M., , , Journal of Biological Chemistry,
3. Cramping tumours: An old observation about cancer cells may lead to a new treatment
4. A New Way to Fight Cancer?
5. DCA Research Information Evangelos Michelakis

Further reading

★ On the Origin of Cancer Cells, O. Warburg, , , Science,

★ Oxidative metabolism in cancer growth, Ristow, M., , , Curr Opin Clin Nutr Metab Care.,

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★ Why do cancers have high aerobic glycolysis?, R. A. Gatenby and R. J. Gillies, , , Nat Rev Cancer, 2004

★ Glycolysis inhibition for anticancer treatment, H. Pelicano, D. S. Martin, R. H. Xu and P. Huang, , , Oncogene,

★ The Warburg hypothesis fifty years later, S. Weinhouse, , , Journal of Cancer Research and Clinical Oncology, 1976

★ Energy Boost: The Warburg Effect Returns in a New Theory of Cancer, Ken Garber, , , Journal of the National Cancer Institute, 2004

★ "Targeting energy metabolism in brain cancer: review and hypothesis," Thomas N Seyfried and Purna Mukherjee, Biology Department, Boston College, Chestnut Hill, MA 02467, USA