Understanding the Warburg Effect Yields New Insights into the Metabolic Control of Cancer

• Hassan Bahrami

  Independent Health/Nutrition Researcher

  https://orcid.org/0000-0003-0755-5714

• Majid Tafrihi

  Molecular and Cell Biology Research Laboratory, Department of Molecular and Cell Biology, Faculty of Sciences, University of Mazandaran, Babolsar, Iran

  https://orcid.org/0000-0001-7200-4252

Human cells may use either aerobic or anaerobic cellular respiration processes to produce energy, depending on cellular conditions. When there is enough oxygen, cells respire aerobically, but in case of oxygen deficiency, anaerobic cellular respiration is used, which leads to lactic acidosis and an increased risk of cancer according to Warburg's hypothesis.

This paper reviews key aspects related to the historical evolutionary origins of metabolic pathways in cancer cells and compares similarities between cancer cells and ancient unicellular organisms to address the origins of metabolic change in cancer cells and provide new insights into the metabolic control of cancer.

Understanding the main causes of cancer and the biological origin of their behavioral abnormalities is essential for the metabolic control of cancer. Environmental stressors to cells may include lack of essential nutrients, poor oxygenation, excess acids, viruses, infections, and exposure to chemicals, toxins, and radiation. These cellular stressors can cause normal cells to mutate and become cancerous in an attempt to survive in the harsh conditions.

According to the research findings, creating appropriate conditions at the cellular level in terms of pH, sufficient oxygenation and the availability of good sugars, essential vitamins, minerals, enzymes and coenzymes through a healthy diet can lead to a metabolic switch in cancer cells that controls mutations, which can help prevent and control cancer.

Jheeta S. The Landscape of the Emergence of Life. Life (Basel) 2017; 7(2): 27. https://doi.org/10.3390/life7020027

Kunnev D. Origin of Life: The Point of No Return. Life 2020; 10(11): 269. https://doi.org/10.3390/life10110269

Kump L. The rise of atmospheric oxygen. Nature 2008; 451: 277-278. https://doi.org/10.1038/nature06587

Olson KR, Straub KD. The Role of Hydrogen Sulfide in Evolution and the Evolution of Hydrogen Sulfide in Metabolism and Signaling. Journal of Physiology 2015; 31(1): 2-72. https://doi.org/10.1152/physiol.00024.2015

West JB. The strange history of atmospheric oxygen. Physiol Rep 2022; 10(6): e15214. https://doi.org/10.14814/phy2.15214

Zhang XJ. Comprehensive Water Quality and Purification 2014; 3: 108-122. Elsevier Inc. ISBN 978-0-12-382183-6. https://doi.org/10.1016/B978-0-12-382182-9.00046-3

Plant JA, Saunders AD. Radiation Protection Dosimetry 1996; 68(1-2): 25-36. https://doi.org/10.1093/oxfordjournals.rpd.a031847

Cockell CS, Raven JA. Ozone and life on the Archaean Earth. Philos Trans A Math Phys Eng Sci 2007; 365(1856): 1889-901. https://doi.org/10.1098/rsta.2007.2049

Ershov B. Natural Radioactivity and Chemical Evolution on the Early Earth: Prebiotic Chemistry and Oxygenation. Molecules 2022; 27(23): 8584. https://doi.org/10.3390/molecules27238584

Gregory TR. Understanding Natural Selection: Essential Concepts and Common Misconceptions. Evo Edu Outreach 2009; 2: 156-175. https://doi.org/10.1007/s12052-009-0128-1

Schirrmeister BE, Gugger M, Donoghue PC. Cyanobacteria and the Great Oxidation Event: evidence from genes and fossils. Palaeontology 2015; 58(5): 769-785. https://doi.org/10.1111/pala.12178

Ma'ayan A. Complex systems biology. J R Soc Interface 2017; 142017039120170391. https://doi.org/10.1098/rsif.2017.0391

Bich L, Pradeu T, Moreau JF. Understanding Multicellularity: The Functional Organization of the Intercellular Space. Front Physiol 2019; 10: 1170. https://doi.org/10.3389/fphys.2019.01170

Cooper MG, Housman RE. The Cell: A Molecular Approach Fifth Edition, Publisher: Sinauer Associates, Inc. 2009; (ISBN-13: 978-0878933006).

Rasnitsyn A. Cancer: A Throwback to Ancient Cells? 2019. https://torontoriot.com/2019/11/26/cancer-a-throwback-to-ancient-cells/

National Cancer Institute. What Is Cancer? 2021. https://www.cancer.gov/about-cancer/understanding/what-is-cancer

Warburg O. On the Origin of Cancer Cells. Science 1956; 123(3191): 309-314. https://doi.org/10.1126/science.123.3191.309

Bahrami H, Tafrihi M, Mohamadzadeh S. Reversing the Warburg effect to control cancer: A review of diet-based solutions. Journal of Current Oncology and Medical Sciences 2022; 2(3). https://submission.journalofcoms.com/ index.php/JCOMS/article/view/54

Bahrami H, Greiner T. The alkaline diet and the Warburg effect. World Nutrition 2021; 12(1): 20-39. https://doi.org/10.26596/wn.202112120-39

Theofilidis G, Bogdanis GC, Koutedakis Y, Karatzaferi C. Monitoring Exercise-Induced Muscle Fatigue and Adaptations: Making Sense of Popular or Emerging Indices and Biomarkers. Sports (Basel) 2018; 6(4): 153. https://doi.org/10.3390/sports6040153

Edwards G. Uranium: Known Facts and Hidden Dangers. The World Uranium Hearing conference, Salzburg 1992.

Isaacs T. What Causes Cancer and What Is it Really? 2016. [Online]. Available at: https://thetruthaboutcancer.com/what-causes-cancer/

Aranda-Anzaldo A, Dent MAR. Is cancer a disease set up by cellular stress responses? Cell Stress Chaperones 2021; 26(4): 597-609. https://doi.org/10.1007/s12192-021-01214-4

Drochioiu G. The influence of respiratory and pH imbalance in cancer development. International Journal of Biochemistry Research and Review 2014; 4(5): 386-409. https://doi.org/10.9734/IJBCRR/2014/8617

Laconi E, Marongiu F, DeGregori J. Cancer as a disease of old age: changing mutational and microenvironmental landscapes. Br J Cancer 2020; 122(7): 943-952. https://doi.org/10.1038/s41416-019-0721-1

International Agency for Research on Cancer. Cancer incidence rate data tables and maps for each country 2020. [Online]. Available at: https://gco.iarc.fr/today/

Bahrami H, Tafrihi M. Global Trends of Cancer: The Role of Diet, Life Style, and Environmental Factors. Cancer Innovation 2023. https://doi.org/10.1002/cai2.76

Schwingshackl L, Morze J, Hoffmann G. Mediterranean diet and health status: Active ingredients and pharmacological mechanisms. Br J Pharmacol 2020; 177(6): 1241-1257. https://doi.org/10.1111/bph.14778

Maruca A, Catalano R, Bagetta D, Mesiti F, Ambrosio FA, Romeo I, Moraca F, Rocca R, Ortuso F, Artese A, Costa G, Alcaro S, Lupia A. The Mediterranean Diet as source of bioactive compounds with multi-targeting anti-cancer profile. European Journal of Medicinal Chemistry 2019; 181: 111579. https://doi.org/10.1016/j.ejmech.2019.111579

O’Keefe SJ. Fat, fiber and cancer risk in African Americans and rural Africans. Nature Communications 2015. https://doi.org/10.1038/ncomms7342

• PDF

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.