The Curcumin Analog Go-Y030 Controls The Generation And Stability Of Regulatory T Cells

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-beta), which promotes the generation of Foxp3(+) Tregs from naive CD4(+) T cells in the local tumor microenvironment. TGF-beta activates nuclear factor kappa B (NF-kappa B)/p300 and SMAD signaling, which increases the number of acetylated histones at the Foxp3 locus and induces Foxp3 gene expression. TGF-beta also helps stabilize Foxp3 expression. The curcumin analog and antitumor agent, GO-Y030, prevented the TGF-beta-induced generation of Tregs by preventing p300 from accelerating NF-kappa B-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-beta. 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.