Sunitinib, a Clinically Used Anticancer Drug, Is a Potent AChE Inhibitor and Attenuates Cognitive Impairments in Mice

Ling Huang, Jiajia Lin, Siying Xiang, Kangrong Zhao, Jie Yu, Jiacheng Zheng, Daping Xu, Shinghung Mak, Shengquan Hu, Shehani Nirasha, Chuang Wang, Xiaowei Chen, Junfang Zhang, Shujun Xu, Xiaofei Wei, Zaijun Zhang, Dongsheng Zhou, Wenhua Zhou, Wei Cui, Yifan HanZhenyu Hu, Qinwen Wang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

19 Citations (Scopus)

Abstract

Sunitinib, a tyrosine kinase inhibitor, is clinically used for the treatment of cancer. In this study, we found for the first time that sunitinib inhibits acetylcholinesterase (AChE) at submicromolar concentrations in vitro. In addition, sunitinib dramatically decreased the hippocampal and cortical activity of AChE in a time-dependent manner in mice. Molecular docking analysis further demonstrates that sunitinib might interact with both the catalytic anion and peripheral anionic sites within AChE, which is in accordance with enzymatic activity results showing that sunitinib inhibits AChE in a mixed pattern. Most importantly, we evaluated the effects of sunitinib on scopolamine-induced cognitive impairments in mice by using novel object recognition and Morris water maze tests. Surprisingly, sunitinib could attenuate cognitive impairments to a similar extent as donepezil, a marketed AChE inhibitor used for the treatment of Alzheimer's disease. In summary, our results have shown that sunitinib could potently inhibit AChE and attenuate cognitive impairments in mice.
Original languageEnglish
Pages (from-to)1047-1056
Number of pages10
JournalACS Chemical Neuroscience
Volume7
Issue number8
DOIs
Publication statusPublished - 17 Aug 2016

Keywords

  • AChE
  • Alzheimer's disease
  • cancer
  • cognitive impairments
  • sunitinib

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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