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抗代谢物和抗癌药物2-脱氧葡萄糖对真核癌症模型芽殖酵母和裂殖酵母的多方面影响。

Multifaceted effects of antimetabolite and anticancer drug, 2-deoxyglucose on eukaryotic cancer models budding and fission yeast.

作者信息

Vishwanatha Akshay, D'Souza Cletus Joseph Michael

机构信息

Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, India.

出版信息

IUBMB Life. 2017 Mar;69(3):137-147. doi: 10.1002/iub.1599. Epub 2017 Jan 17.

DOI:10.1002/iub.1599
PMID:28093891
Abstract

Glycolytic inhibitors are of interest therapeutically as they are effective against cancers that display increased glycolytic rate and mitochondrial defects. 2-Deoxyglucose (2-DG) is one such glycolytic inhibitor and was identified to be a competitive inhibitor of glucose. Studies from past few decades have shown that the mechanism of action of 2-DG is complex involving several metabolic and signaling pathways. Budding yeast Saccharomyces cerevisiae and fission yeast Schizosaccharomyces pombe are two important models for studying metabolism, cell cycle and cell signaling. These two unicellular eukaryotes are Crabtree positive yeasts exhibiting a metabolism similar to that of cancer cells. Effects of 2-DG in yeast is of interest owing to these similarities and hence yeasts have emerged as ideal model organisms to study the mode of action and resistance to 2-DG. In this review, we summarize the studies on biological effect and resistance to 2-DG in budding and fission yeasts and give an insight into its possible mechanism of action as models for understanding cancer metabolism and drugs affecting cancer progression. © 2017 IUBMB Life, 69(3):137-147, 2017.

摘要

糖酵解抑制剂在治疗方面具有重要意义,因为它们对糖酵解速率增加和线粒体缺陷的癌症有效。2-脱氧葡萄糖(2-DG)就是这样一种糖酵解抑制剂,它被确定为葡萄糖的竞争性抑制剂。过去几十年的研究表明,2-DG的作用机制很复杂,涉及多个代谢和信号通路。出芽酵母酿酒酵母和裂殖酵母粟酒裂殖酵母是研究代谢、细胞周期和细胞信号传导的两个重要模型。这两种单细胞真核生物是克氏阳性酵母,其代谢方式与癌细胞相似。由于这些相似性,2-DG对酵母的影响备受关注,因此酵母已成为研究2-DG作用模式和抗性的理想模式生物。在这篇综述中,我们总结了关于出芽酵母和裂殖酵母中2-DG的生物学效应和抗性的研究,并深入探讨了其作为理解癌症代谢和影响癌症进展的药物的模型的可能作用机制。© 2017国际生物化学与分子生物学联盟生命科学,69(3):137 - 147,2017。

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