Diaz-Ruiz R, Uribe-Carvajal S, Devin A, Rigoulet M
CNRS, Institute of Biochemistry and Genetics of the Cell (IBGC), UMR 5095, 1 rue Camille Saint Saëns, 33077 Bordeaux cedex, France.
Biochim Biophys Acta. 2009 Dec;1796(2):252-65. doi: 10.1016/j.bbcan.2009.07.003. Epub 2009 Aug 12.
During the last decades a considerable amount of research has been focused on cancer. A number of genetic and signaling defects have been identified. This has allowed the design and screening of a number of anti-tumor drugs for therapeutic use. One of the main challenges of anti-cancer therapy is to specifically target these drugs to malignant cells. Recently, tumor cell metabolism has been considered as a possible target for cancer therapy. It is widely accepted that tumors display an enhanced glycolytic activity and oxidative phosphorylation down-regulation (Warburg effect). Therefore, it seems reasonable that disruption of glycolysis might be a promising candidate for specific anti-cancer therapy. Nonetheless, the concept of aerobic glycolysis as the paradigm of tumor cell metabolism has been challenged, as some tumor cells use oxidative phosphorylation. Mitochondria are of special interest in cancer cell energy metabolism, as their physiology is linked to the Warburg effect. Besides, their central role in apoptosis makes these organelles a promising "dual hit target" for selectively eliminate tumor cells. Thus, it is desirable to have an easy-to-use and reliable model in order to do the screening for energy metabolism-inhibiting drugs to be used in cancer therapy. From a metabolic point of view, the fermenting yeast Saccharomyces cerevisiae and tumor cells share several features. In this paper we will review these common metabolic properties and we will discuss the possibility of using S. cerevisiae as an early screening test in the research for novel anti-tumor compounds used for the inhibition of tumor cell metabolism.
在过去几十年中，大量研究聚焦于癌症。已识别出许多基因和信号缺陷。这使得能够设计和筛选多种用于治疗的抗肿瘤药物。抗癌治疗的主要挑战之一是将这些药物特异性地靶向恶性细胞。最近，肿瘤细胞代谢被认为是癌症治疗的一个可能靶点。人们普遍认为肿瘤表现出增强的糖酵解活性和氧化磷酸化下调（瓦伯格效应）。因此，破坏糖酵解可能是特异性抗癌治疗的一个有前景的候选方法，这似乎是合理的。尽管如此，有氧糖酵解作为肿瘤细胞代谢范例的概念受到了挑战，因为一些肿瘤细胞利用氧化磷酸化。线粒体在癌细胞能量代谢中特别受关注，因为其生理学与瓦伯格效应相关。此外，它们在细胞凋亡中的核心作用使这些细胞器成为选择性消除肿瘤细胞的一个有前景的“双靶点”。因此，可以期望有一个易于使用且可靠的模型，以便筛选用于癌症治疗的能量代谢抑制药物。从代谢角度来看，发酵酵母酿酒酵母和肿瘤细胞有几个共同特征。在本文中，我们将综述这些共同的代谢特性，并讨论使用酿酒酵母作为早期筛选试验来研究用于抑制肿瘤细胞代谢的新型抗肿瘤化合物的可能性。
