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

11 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

Bibliographical note

Funding Information:
We thank the HTS core facility of Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center. This study was supported by the Grants from the Korean Healthy Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI17C0501); MRC grant (2018R1A5A2020732) funded by the Korean government (MSIT).

Funding Information:
We thank the HTS core facility of Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center. This study was supported by the Grants from the Korean Healthy Technology R&D Project, Ministry of Health & Welfare, Republic of Korea ( HI17C0501 ); MRC grant ( 2018R1A5A2020732 ) funded by the Korean government ( MSIT ).

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

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

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