PMID- 33339133
OWN - NLM
STAT- MEDLINE
DCOM- 20210315
LR  - 20210315
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 24
DP  - 2020 Dec 16
TI  - Resveratrol Activates Natural Killer Cells through Akt- and mTORC2-Mediated c-Myb 
      Upregulation.
LID - 10.3390/ijms21249575 [doi]
LID - 9575
AB  - Natural killer (NK) cells are suitable targets for cancer immunotherapy owing to 
      their potent cytotoxic activity. To maximize the therapeutic efficacy of cancer 
      immunotherapy, adjuvants need to be identified. Resveratrol is a well-studied 
      polyphenol with various potential health benefits, including antitumor effects. 
      We previously found that resveratrol is an NK cell booster, suggesting that it 
      can serve as an adjuvant for cancer immunotherapy. However, the molecular 
      mechanism underlying the activation of NK cells by resveratrol remains unclear. 
      The present study aimed to determine this mechanism. To this end, we investigated 
      relevant pathways in NK cells using Western blot, real-time polymerase chain 
      reaction, pathway inhibitor, protein/DNA array, and cytotoxicity analyses. We 
      confirmed the synergistic effects of resveratrol and interleukin (IL)-2 on 
      enhancing the cytolytic activity of NK cells. Resveratrol activated Akt by 
      regulating Mammalian Target of Rapamycin (mTOR) Complex 2 (mTORC2) via 
      phosphatase and tensin homolog (PTEN) and ribosomal protein S6 kinase beta-1 
      (S6K1). Moreover, resveratrol-mediated NK cell activation was more dependent on 
      the mTOR pathway than the Akt pathway. Importantly, resveratrol increased the 
      expression of c-Myb, a downstream transcription factor of Akt and mTORC2. 
      Moreover, c-Myb was essential for resveratrol-induced NK cell activation in 
      combination with IL-2. Our results demonstrate that resveratrol activates NK 
      cells through Akt- and mTORC2-mediated c-Myb upregulation.
FAU - Lee, Yoo-Jin
AU  - Lee YJ
AUID- ORCID: 0000-0003-3895-9236
AD  - Department of Microbiology and Institute for Immunology and Immunological 
      Diseases, Yonsei University College of Medicine, Seoul 08758, Korea.
AD  - Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of 
      Medicine, Seoul 08758, Korea.
FAU - Kim, Jongsun
AU  - Kim J
AD  - Department of Microbiology and Institute for Immunology and Immunological 
      Diseases, Yonsei University College of Medicine, Seoul 08758, Korea.
LA  - eng
GR  - 2016-31-0446/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20201216
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Proto-Oncogene Proteins c-myb)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Cell Line
MH  - Humans
MH  - Killer Cells, Natural/*drug effects/immunology
MH  - *Lymphocyte Activation
MH  - Mechanistic Target of Rapamycin Complex 2/metabolism
MH  - PTEN Phosphohydrolase/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Proto-Oncogene Proteins c-myb/genetics/*metabolism
MH  - Resveratrol/*pharmacology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Up-Regulation
PMC - PMC7765583
OTO - NOTNLM
OT  - Akt
OT  - NK cells
OT  - c-Myb
OT  - mTOR complex 2
OT  - resveratrol
COIS- The authors declare no conflict of interest.
EDAT- 2020/12/20 06:00
MHDA- 2021/03/16 06:00
PMCR- 2020/12/16
CRDT- 2020/12/19 01:01
PHST- 2020/12/07 00:00 [received]
PHST- 2020/12/11 00:00 [revised]
PHST- 2020/12/14 00:00 [accepted]
PHST- 2020/12/19 01:01 [entrez]
PHST- 2020/12/20 06:00 [pubmed]
PHST- 2021/03/16 06:00 [medline]
PHST- 2020/12/16 00:00 [pmc-release]
AID - ijms21249575 [pii]
AID - ijms-21-09575 [pii]
AID - 10.3390/ijms21249575 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Dec 16;21(24):9575. doi: 10.3390/ijms21249575.