2. Academic Validation
  3. A natural product, Piperlongumine (PL), increases tumor cells sensitivity to NK cell killing

A natural product, Piperlongumine (PL), increases tumor cells sensitivity to NK cell killing

  • Int Immunopharmacol. 2021 Jul;96:107658. doi: 10.1016/j.intimp.2021.107658.
Lukman O Afolabi 1,  Jiacheng Bi 2,  Liang Chen 1,  Xiaochun Wan 3
Affiliations

Affiliations

  • 1 Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China; University of Chinese Academy of Sciences, Beijing 100864, PR China.
  • 2 Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China; University of Chinese Academy of Sciences, Beijing 100864, PR China.
  • 3 Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China; University of Chinese Academy of Sciences, Beijing 100864, PR China. Electronic address: xc.wan@siat.ac.cn.
PMID: 33887610 DOI: 10.1016/j.intimp.2021.107658
Abstract

Natural Killer (NK) cells are components of innate immune surveillance against transformed cells. NK cell immunotherapy has attracted attention as a promising strategy for Cancer treatment, whose antitumor effects, however, require further improvement. The use of small molecules with immunomodulatory potentials and selective tumor-killing possesses the potential to complement immunotherapy. This study demonstrated that Piperlongumine (PL), a natural alkaloid obtained from long pepper fruit, alone has antitumor and anti-proliferative potential on all the tested tumors in vitro. PL pretreatment of tumor cells also potentiates their susceptibility to NK cell cytolysis at the doses where NK cell functions were preserved. Importantly, PL suppresses both NK -sensitive MHC-I -deficient and MHC-I -sufficient tumor growth in vivo. Mechanistically, PL induces misfolded proteins, impedes Autophagy, increases ROS and tumor conjugation with NK cells. Furthermore, PL enhances the expression of NK cell-activating receptors on NK cells and its ligands on tumor cells, possibly leading to increased susceptibility to NK cell killing. Our findings showed the antitumor and immunomodulatory potential of PL, which could be explored to complement NK cell immunotherapy for Cancer treatment.

Keywords

Cancer; Cytotoxicity; Immunomodulators; Natural Killer cell; Piperlongumine.

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