Department of Physiology, University of Pretoria, Private Bag X323, Arcadia, Pretoria, 0007, South Africa.
Arch Pharm Res. 2019 Oct;42(10):833-847. doi: 10.1007/s12272-019-01185-2. Epub 2019 Aug 31.
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.
葡萄糖是能量产生中的关键分子，在非致瘤性和致瘤性组织代谢中产生不同的终产物。致瘤细胞通过发酵氧化葡萄糖，即使在有氧气的情况下也会产生乳酸盐和三磷酸腺苷（瓦博格效应）。Na+/H+反向转运蛋白在致瘤细胞中上调，导致乳酸盐和 H+离子释放到细胞外空间。乳酸盐和质子离子在细胞外空间的积累导致酸性环境，促进侵袭和转移。奥托·瓦伯格（Otto Warburg）报告说，致瘤细胞的线粒体有缺陷，产生的能量较少。然而，几十年后，很明显这些线粒体已经通过改变线粒体的含量、结构、功能和活性进行了适应。线粒体生物发生和自噬调节新的线粒体的形成和有缺陷的线粒体的降解，以对抗突变性线粒体脱氧核糖核酸的积累。致瘤细胞还产生增加的活性氧物种（ROS），这是由于糖酵解的上调导致包括癌症在内的发病机制。适度的 ROS 水平发挥增殖和生存信号作用，而高 ROS 数量则诱导细胞死亡。了解异常代谢、氧化还原调节、线粒体适应和 pH 调节之间的相互作用，为科学界和医学界提供了新的机会来探索癌症治疗方法。
