Department of Laboratory Medicine, Catholic University, Rome, Italy.
Adv Exp Med Biol. 2012;942:287-308. doi: 10.1007/978-94-007-2869-1_13.
At the beginning of the twentieth century, Otto Warburg demonstrated that cancer cells have a peculiar metabolism. These cells preferentially utilise glycolysis for energetic and anabolic purposes, producing large quantities of lactic acid. He defined this unusual metabolism "aerobic glycolysis". At the same time, Warburg hypothesised that a disruption of mitochondrial activities played a precise pathogenic role in cancer. Because of this so-called "Warburg effect", mitochondrial physiology and cellular respiration in particular have been overlooked in pathophysiological studies of cancer. Over time, however, many studies have shown that mitochondria play a fundamental role in cell death by apoptosis or necrosis. Moreover, metabolic enzymes of the Krebs cycle have also recently been recognised as oncosuppressors. Recently, a series of studies were undertaken to re-evaluate the role of oxidative mitochondrial metabolism in cancer cell growth and progression. Some of these data indicate that modulation of mitochondrial respiration may induce an arrest of cancer cell proliferation and differentiation (pseudodifferentiation) and/or or death, suggesting that iatrogenic manipulation of some mitochondrial activities may induce anticancer effects. Moreover, studying the role of mitochondria in cancer cell dedifferentiation/differentiation processes may allow further insight into the pathophysiology and therapy of so-called cancer stem cells.
二十世纪初，奥托·瓦尔堡（Otto Warburg）证实癌细胞具有特殊的代谢方式。这些细胞优先利用糖酵解作用来获取能量和合成代谢物，从而产生大量乳酸。他将这种异常代谢方式定义为“有氧糖酵解”。同时，瓦尔堡假设线粒体活动的破坏在癌症的发病机制中起着精确的致病作用。由于这种所谓的“瓦伯格效应”，线粒体生理学和细胞呼吸在癌症的病理生理学研究中一直被忽视。然而，随着时间的推移，许多研究表明，线粒体在细胞凋亡或坏死的细胞死亡中起着根本作用。此外，克雷布斯循环的代谢酶最近也被认为是肿瘤抑制因子。最近，人们进行了一系列研究来重新评估氧化线粒体代谢在癌细胞生长和进展中的作用。其中一些数据表明，调节线粒体呼吸可能会诱导癌细胞增殖和分化（假性分化）和/或死亡的停滞，这表明人为地操纵某些线粒体活动可能会诱导抗癌作用。此外，研究线粒体在癌细胞去分化/分化过程中的作用可能会进一步深入了解所谓的癌症干细胞的病理生理学和治疗。
