2. Academic Validation
  3. Cycloartenyl ferulate improves natural killer (NK) cell immunity against cancer by binding to IFNγ receptor 1

Cycloartenyl ferulate improves natural killer (NK) cell immunity against cancer by binding to IFNγ receptor 1

  • J Biol Chem. 2023 Jun 29;104990. doi: 10.1016/j.jbc.2023.104990.
Mingfeng Li 1,  Aotong Zhang 1,  Yanqing Wang 2,  Jiaxin Chen 1,  Xin Qi 1,  Yuanren Ma 1,  Chunxiao Huang 1,  Ying Xiong 3,  Xiaomin Zhang 1,  Wenjiao Xia 1,  Dehai Li 1,  Yankai Liu 1,  Zhicheng Zuo 4,  Jing Li 5
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, P. R. China.
  • 2 College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai Frontiers Science Research Center for Druggability of Cardiovascular noncoding RNA, Institute for Frontier Medical Technology, Shanghai University of Engineering Science, Shanghai, 201620, P. R. China.
  • 3 School of Pharmacy, Fudan University, Shanghai, 201203, China.
  • 4 College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai Frontiers Science Research Center for Druggability of Cardiovascular noncoding RNA, Institute for Frontier Medical Technology, Shanghai University of Engineering Science, Shanghai, 201620, P. R. China. Electronic address: ZhichengZuo@sues.edu.cn.
  • 5 Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, P. R. China. Electronic address: lijing_ouc@ouc.edu.cn.
PMID: 37392850 DOI: 10.1016/j.jbc.2023.104990
Abstract

Cycloartenyl ferulate (CF) is abundant in brown rice with multiple biological-functions. It has been reported to possess antitumor activity, however, the related action mechanism of action of CF has not been clarified. Herein, we unexpectedly uncover the immunological regulation effects of CF and its molecular mechanism. We discovered that CF directly enhanced the killing capacity of natural killer (NK) cells for various Cancer cells in vitro. In vivo, CF also improved Cancer surveillance in mouse models of lymphoma clearance and metastatic melanoma dependent on NK cells. In addition, CF promoted Anticancer efficacy of the anti-PD1 antibody with improvement of tumor immune microenvironment. Mechanistically, we first unveiled that CF acted on the canonical JAK1/2-STAT1 signaling pathway to enhance the immunity of the NK cells by selectively binding to IFNγ receptor 1 (IFNγR1). Collectively, our results indicate that CF is a promising immunoregulation agent worthy of attention in clinical application in the future. Due to broad biological significance of IFNγ, our findings also provide a capability to understand the diverse functions of CF.

Keywords

Cancer; Cycloartenyl ferulate; IFNγ receptor; Immunology; NK cell; Signaling pathway.

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