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- 저자 : Maphuti T. Lebelo (검색결과 1 건)
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Warburg effect and its role in tumourigenesis
Maphuti T. Lebelo,Anna M. Joubert,Michelle H. Visagie 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.10
Glucose is a crucial molecule in energy productionand produces different end products in non-tumourigenic-and tumourigenic tissue metabolism. Tumourigeniccells oxidise glucose by fermentation and generate lactateand adenosine triphosphate even in the presence of oxygen(Warburg effect). The Na+/H+-antiporter is upregulated intumourigenic cells resulting in release of lactate- and H+ions into the extracellular space. Accumulation of lactateandproton ions in the extracellular space results in an acidicenvironment that promotes invasion and metastasis. OttoWarburg reported that tumourigenic cells have defectivemitochondria that produce less energy. However, decadeslater it became evident that these mitochondria have adaptedwith alterations in mitochondrial content, structure, functionand activity. Mitochondrial biogenesis and mitophagyregulate the formation of new mitochondria and degradationof defective mitochondria in order to combat accumulationof mutagenic mitochondrial deoxyribonucleic acid. Tumourigenic cells also produce increase reactive oxygenspecies (ROS) resulting from upregulated glycolysis leadingto pathogenesis including cancer. Moderate ROS levelsexert proliferative- and prosurvival signaling, while highROS quantities induce cell death. Understanding the crosstalkbetween aberrant metabolism, redox regulation, mitochondrialadaptions and pH regulation provides scientificandmedical communities with new opportunities to explorecancer therapies.
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