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The phrase "Warburg effect" is used for two unrelated observations in biochemistry, one in plant physiology and the other in oncology, both due to Nobel laureate Otto Heinrich Warburg.

Physiology

In plant physiology, the Warburg effect is the inhibition of carbon dioxide fixation, and subsequently of photosynthesis, by high oxygen concentrations. The oxygenase activity of RuBisCO, which initiates the process of photorespiration, largely accounts for this effect.

Oncology

Basis

In oncology, the Warburg effect is the observation that most cancer cells predominantly produce energy by glycolysis followed by lactic acid fermentation in the cytosol, rather than by oxidation of pyruvate in mitochondria like most normal cells. This occurs even if oxygen is plentiful. Otto Warburg postulated that this change in metabolism is the fundamental cause of cancer, a claim now known as the Warburg hypothesis. Today it is thought that genetic mutations are the fundamental cause of cancer. The Warburg effect may simply be a consequence of damage to the mitochondria in cancer, or an adaptation to low-oxygen environments within tumors, or a result of cancer genes shutting down the mitochondria because they are involved in the cell's apoptosis program which would otherwise kill cancerous cells.

Potential for Cancer Treatment

On 16 March 2008 it was reported that Harvard Medical School announced that they had identified the enzyme that gave rise to the Warburg Effect.

HMS researchers stated that a particular form of pyruvate kinase, namely M2-PK, was responsible for enabling cancer cells to consume glucose at an accelerated rate, and on forcing the cells to switch to pyruvate kinase's alternative form by inhibiting the production of PKM2, their growth was curbed.

They also demonstrated that on introducing the cells to laboratory mice, their ability to devlope tumours was severely compromised.

The researchers acknowledged the fact that the exact chemistry of glucose metabolism was likely to vary across different forms of cancer, however PKM2 was identified in all of the cancer cells they had experimented upon and is not usually present in healthy tissue, indicating that treatment via this route may afford optimistic results.

The use of dichloroacetic acid for cancer treatment using this methodology was published by researchers at the University of Alberta in January 2007. Trials are continuing.

References

1. Warburg O (1956). "On the origin of cancer cells". Science. 123 (3191): 309–14. doi:10.1126/science.123.3191.309. PMID 13298683.
2. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC (2008). "The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth". Nature. 452 (7184): 230–3. doi:10.1038/nature06734. PMID 18337823.{{cite journal}}: CS1 maint: multiple names: authors list (link)
3. Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED (2007). "A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth". Cancer Cell. 11 (1): 37–51. doi:10.1016/j.ccr.2006.10.020. PMID 17222789.{{cite journal}}: CS1 maint: multiple names: authors list (link)
4. Pan JG, Mak TW (2007). "Metabolic targeting as an anticancer strategy: dawn of a new era?". Sci. STKE. 2007 (381): pe14. doi:10.1126/stke.3812007pe14. PMID 17426345.
5. Pearson H (2007). "Cancer patients opt for unapproved drug". Nature. 446 (7135): 474–5. doi:10.1038/446474a. PMID 17392750.

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