Ristow Michael
Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany.
Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):339-45. doi: 10.1097/01.mco.0000232892.43921.98.
Recent evidence suggests that oxidative metabolism may have a key role in controlling cancer growth. This review will provide an overview of the evidence accumulated so far. More than 80 years ago, Otto Warburg suggested that impaired oxidative metabolism may cause malignant growth. This assumption, later known as Warburg's hypothesis, has been experimentally addressed for many decades. It employs multiple approaches including cell lines, implanted xenografts and other animal models, by biochemical methods to quantify glycolytic and mitochondrial fluxes and signaling pathways including the rates of intermediate metabolism, respiration and oxidative phosphorylation.
The hallmarks of cancer growth, increased glycolysis and lactate production in tumors, have raised attention recently due to novel observations suggesting a wide spectrum of oxidative phosphorylation deficits and decreased availability of ATP associated with malignancies and tumor cell expansion. The most recent findings suggest that forcing cancer cells into mitochondrial metabolism efficiently suppresses cancer growth, and that impaired mitochondrial respiration may even have a role in metastatic processes.
This review summarizes published evidence on the essential interaction of tumor growth and mitochondrial metabolism, implicating novel approaches for the prevention and treatment of malignant disease.
最近的证据表明，氧化代谢可能在控制癌症生长中起关键作用。本综述将概述迄今为止积累的证据。80多年前，奥托·瓦尔堡提出氧化代谢受损可能导致恶性生长。这一假设，后来被称为瓦尔堡假说，几十年来一直在通过实验进行研究。它采用多种方法，包括细胞系、植入的异种移植物和其他动物模型，通过生化方法来量化糖酵解和线粒体通量以及信号通路，包括中间代谢、呼吸和氧化磷酸化的速率。
癌症生长的标志，即肿瘤中糖酵解增加和乳酸生成增加，最近引起了关注，因为新的观察结果表明存在广泛的氧化磷酸化缺陷以及与恶性肿瘤和肿瘤细胞扩张相关的ATP可用性降低。最新研究结果表明，迫使癌细胞进入线粒体代谢可有效抑制癌症生长，线粒体呼吸受损甚至可能在转移过程中起作用。
本综述总结了已发表的关于肿瘤生长与线粒体代谢的重要相互作用的证据，涉及预防和治疗恶性疾病的新方法。
