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题名Aldo-keto reductases-mediated cytotoxicity of 2-deoxyglucose: A novel anticancer mechanism
作者
发表日期2018-06-01
发表期刊Cancer Science
ISSN/eISSN1347-9032
卷号109期号:6页码:1970-1980
摘要

2-Deoxyglucose (2DG) is a non-metabolizable glucose analog currently in clinical trials to determine its efficacy in enhancing the therapeutic effects of radiotherapy and chemotherapy of several types of cancers. It is thought to preferentially kill cancer cells by inhibiting glycolysis because cancer cells are more dependent on glycolysis for their energy needs than normal cells. However, we found that the toxicity of 2DG in cancer cells is mediated by the enzymatic activities of AKR1B1 and/or AKR1B10 (AKR1Bs), which are often overexpressed in cancer cells. Our results show that 2DG kills cancer cells because, in the process of being reduced by AKR1Bs, depletion of their cofactor NADPH leads to the depletion of glutathione (GSH) and cell death. Furthermore, we showed that compounds that are better substrates for AKR1Bs than 2DG are more effective than 2DG in killing cancer cells that overexpressed these 2 enzymes. As cancer cells can be induced to overexpress AKR1Bs, the anticancer mechanism we identified can be applied to treat a large variety of cancers. This should greatly facilitate the development of novel anticancer drugs.

关键词2-deoxyglucose AKR1B1 AKR1B10 glutathione (GSH) oxidative stress
DOI10.1111/cas.13604
URL查看来源
收录类别SCIE
语种英语English
WOS研究方向Oncology
WOS类目Oncology
WOS记录号WOS:000434351000022
Scopus入藏号2-s2.0-85046259781
引用统计
被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符https://repository.uic.edu.cn/handle/39GCC9TT/6309
专题北师香港浸会大学
通讯作者Chung, Sum Man Stephen
作者单位
1.Department of Biology,Hong Kong Baptist University,Hong Kong
2.Division of Science and Technology,United International College,Zhuhai,China
3.Faculty of Medicine,School of Biomedical Sciences,The University of Hong Kong,Hong Kong
第一作者单位北师香港浸会大学
通讯作者单位北师香港浸会大学
推荐引用方式
GB/T 7714
Zhang, Shi Qing,Yung, Kin Lam Ken,Chung, Sookja Kimet al. Aldo-keto reductases-mediated cytotoxicity of 2-deoxyglucose: A novel anticancer mechanism[J]. Cancer Science, 2018, 109(6): 1970-1980.
APA Zhang, Shi Qing, Yung, Kin Lam Ken, Chung, Sookja Kim, & Chung, Sum Man Stephen. (2018). Aldo-keto reductases-mediated cytotoxicity of 2-deoxyglucose: A novel anticancer mechanism. Cancer Science, 109(6), 1970-1980.
MLA Zhang, Shi Qing,et al."Aldo-keto reductases-mediated cytotoxicity of 2-deoxyglucose: A novel anticancer mechanism". Cancer Science 109.6(2018): 1970-1980.
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