The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells

Takashi MaruYama, Shuhei Kobayashi, Hiroko Nakatsukasa, Yuki Moritoki, Daiki Taguchi, Yoichi Sunagawa, Tatsuya Morimoto, Atsuko Asao, Wenwen Jin, Yuji Owada, Naoto Ishii, Yoshiharu Iwabuchi, Akihiko Yoshimura, Wan Jun Chen, Hiroyuki Shibata

Research output: Contribution to journalArticlepeer-review

Abstract

Regulatory T cells (Tregs) play a crucial role in preventing antitumor immune responses in cancer tissues. Cancer tissues produce large amounts of transforming growth factor beta (TGF-β), which promotes the generation of Foxp3+ Tregs from naïve CD4+ T cells in the local tumor microenvironment. TGF-β activates nuclear factor kappa B (NF-κB)/p300 and SMAD signaling, which increases the number of acetylated histones at the Foxp3 locus and induces Foxp3 gene expression. TGF-β also helps stabilize Foxp3 expression. The curcumin analog and antitumor agent, GO-Y030, prevented the TGF-β-induced generation of Tregs by preventing p300 from accelerating NF-κB-induced Foxp3 expression. Moreover, the addition of GO-Y030 resulted in a significant reduction in the number of acetylated histones at the Foxp3 promoter and at the conserved noncoding sequence 1 regions that are generated in response to TGF-β. In vivo tumor models demonstrated that GO-Y030-treatment prevented tumor growth and reduced the Foxp3+ Tregs population in tumor-infiltrating lymphocytes. Therefore, GO-Y030 exerts a potent anticancer effect by controlling Treg generation and stability.

Original languageEnglish
Article number687669
JournalFrontiers in Immunology
Volume12
DOIs
Publication statusPublished - 2021 Jun 23

Keywords

  • Foxp3
  • gene regulating
  • GO-Y030
  • regulatory T cell
  • TGF-beta 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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