发表状态 | 已发表Published |
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
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ISSN/eISSN | 1347-9032 |
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 |
DOI | 10.1111/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 | |
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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