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Warburg effect and its role in tumourigenesis

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Abstract

Glucose is a crucial molecule in energy production and produces different end products in non-tumourigenic- and tumourigenic tissue metabolism. Tumourigenic cells oxidise glucose by fermentation and generate lactate and adenosine triphosphate even in the presence of oxygen (Warburg effect). The Na+/H+-antiporter is upregulated in tumourigenic cells resulting in release of lactate- and H+ ions into the extracellular space. Accumulation of lactate- and proton ions in the extracellular space results in an acidic environment that promotes invasion and metastasis. Otto Warburg reported that tumourigenic cells have defective mitochondria that produce less energy. However, decades later it became evident that these mitochondria have adapted with alterations in mitochondrial content, structure, function and activity. Mitochondrial biogenesis and mitophagy regulate the formation of new mitochondria and degradation of defective mitochondria in order to combat accumulation of mutagenic mitochondrial deoxyribonucleic acid. Tumourigenic cells also produce increase reactive oxygen species (ROS) resulting from upregulated glycolysis leading to pathogenesis including cancer. Moderate ROS levels exert proliferative- and prosurvival signaling, while high ROS quantities induce cell death. Understanding the crosstalk between aberrant metabolism, redox regulation, mitochondrial adaptions and pH regulation provides scientific- and medical communities with new opportunities to explore cancer therapies.

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Fig. 1

Diagram created by M.T. Lebelo in Microsoft Publisher 2013

Fig. 2

Diagram created by M.T. Lebelo in Microsoft Publisher 2013

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Acknowledgements

Funds were provided by Prof. AM Joubert who acquired grants from the National Research Foundation (Grant Nos. N00591, N00375, N00903, N01716), the Cancer Association of South Africa (Grant Nos. AOV741, AOW228), the Struwig Germeshuysen Trust, the School of Medicine Research Committee of the University of Pretoria and Medical Research Council of South Africa. Additional funding was provided by Dr. MH Visagie whom received grants from the National Research Foundation, the School of Medicine Research Committee of the University of Pretoria and Struwig Germeshysen Trust. A special acknowledgement to Dr. TV Mqoco who assisted with subsidies obtained from Thutukha National Research Foundation.

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  1. Department of Physiology, University of Pretoria, Private Bag X323, Arcadia, Pretoria, 0007, South Africa

    Maphuti T. Lebelo, Anna M. Joubert & Michelle H. Visagie

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  1. Maphuti T. Lebelo
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  2. Anna M. Joubert
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Lebelo, M.T., Joubert, A.M. & Visagie, M.H. Warburg effect and its role in tumourigenesis. Arch. Pharm. Res. 42, 833–847 (2019). https://doi.org/10.1007/s12272-019-01185-2

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