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

• Published in: Frontiers in immunology Vol. 12; p. 687669
• Main Authors: MaruYama, Takashi, Kobayashi, Shuhei, Nakatsukasa, Hiroko, Moritoki, Yuki, Taguchi, Daiki, Sunagawa, Yoichi, Morimoto, Tatsuya, Asao, Atsuko, Jin, Wenwen, Owada, Yuji, Ishii, Naoto, Iwabuchi, Yoshiharu, Yoshimura, Akihiko, Chen, WanJun, Shibata, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 23.06.2021
• Subjects: Animals; Antineoplastic Agents, Phytogenic - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Coculture Techniques; Curcumin - analogs & derivatives; Curcumin - pharmacology; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Foxp3; gene regulating; GO-Y030; Immunology; Lymphocyte Activation - drug effects; Lymphocytes, Tumor-Infiltrating - drug effects; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Melanoma, Experimental - drug therapy; Melanoma, Experimental - immunology; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Mice; Mice, Inbred C57BL; Mice, Transgenic; NF-kappa B - metabolism; p300-CBP Transcription Factors - metabolism; regulatory T cell; Skin Neoplasms - drug therapy; Skin Neoplasms - immunology; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; TGF-beta 1; Tumor Burden - drug effects; regulatory T cell; Foxp3; GO-Y030; TGF-beta 1; gene regulating
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.687669

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 locus and induces 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. 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.