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Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
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Resveratrol Activates Natural Killer Cells through Akt- and mTORC2-Mediated c-Myb Upregulation

Yoo-Jin Lee1,2, Jongsun Kim1

  • 1Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 08758, Korea.

International Journal of Molecular Sciences
|December 19, 2020
PubMed

Insights

Resveratrol boosts natural killer (NK) cell activity, acting as a potential cancer immunotherapy adjuvant. This study reveals resveratrol activates NK cells by upregulating c-Myb through the Akt and mTORC2 pathways.

Area of Science:

  • Immunology
  • Cancer Research
  • Pharmacology

Background:

  • Natural killer (NK) cells are crucial for cancer immunotherapy due to their cytotoxic functions.
  • Identifying effective adjuvants is key to enhancing cancer immunotherapy efficacy.
  • Resveratrol, a polyphenol, has demonstrated antitumor properties and previously shown potential as an NK cell booster.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which resveratrol activates NK cells.
  • To investigate the role of Akt, mTORC2, and c-Myb in resveratrol-mediated NK cell activation.
  • To confirm resveratrol's synergistic effect with Interleukin-2 (IL-2) in enhancing NK cell activity.

Main Methods:

  • Western blot analysis
  • Real-time polymerase chain reaction (PCR)
  • Pathway inhibitors
  • Protein/DNA array analysis
  • Cytotoxicity assays
  • Investigated Akt, mTORC2, PTEN, S6K1, and c-Myb expression and activation

Main Results:

  • Resveratrol synergistically enhanced NK cell cytolytic activity with IL-2.
  • Resveratrol activated Akt via regulation of mTORC2, PTEN, and S6K1.
  • Resveratrol-mediated NK cell activation was predominantly dependent on the mTOR pathway.
  • Resveratrol increased the expression of c-Myb, a downstream target of Akt and mTORC2.
  • c-Myb was essential for resveratrol and IL-2-induced NK cell activation.

Conclusions:

  • Resveratrol activates NK cells through a mechanism involving Akt and mTORC2 signaling.
  • Upregulation of c-Myb is a critical step in resveratrol-induced NK cell activation.
  • Resveratrol holds promise as an adjuvant for cancer immunotherapy by enhancing NK cell function.
Keywords:
AktNK cellsc-MybmTOR complex 2resveratrol

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