Direct potentiation of NK cell cytotoxicity by 8-azaguanine with potential antineoplastic activity

Nayoung Kim, Ji Wan Choi, Ah Young Song, Woo Seon Choi, Hye Ran Park, Sojung Park, Inki Kim, Hun Sik Kim

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

This study identified 8-azaguanine (8-AG) as a novel immunomodulatory drug (IMiD) through a high-throughput screen of the Preswick Chemical Library in a model of human NK cell cytotoxicity against blood cancer cells. 8-AG, originally developed as an antineoplastic agent, significantly increased the cytotoxicity of NK cells and was superior in this activity to previously known IMiDs, such as fluoxetine and amphotericin B, identified from the same library. IFN-γ expression was also slightly increased by 8-AG. Mechanistically, 8-AG increased conjugate formation between NK and target cells and subsequent cytolytic granule polarization, but not calcium mobilization, regulation of activating receptors, or expression of perforin or granzyme B. Thus, the antineoplastic activity of 8-AG should be re-evaluated in light of this novel potentiating effect on NK cells.

Original languageEnglish
Pages (from-to)152-159
Number of pages8
JournalInternational Immunopharmacology
Volume67
DOIs
StatePublished - Feb 2019

Keywords

  • 8-azaguanine
  • Cytotoxicity
  • Immunomodulatory drugs
  • Library screening
  • NK cells

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