title: Resveratrol analog, HS-1793 enhance anti-tumor immunity by reducing the CD4+CD25+ regulatory T cells in FM3A tumor bearing mice.
abstract: Natural agents with the immunomodulating property have been gaining traction to be employed in the complementary therapy of cancer because the ineffectiveness of numerous therapeutic strategies may be related in part to the tumor-induced immunosuppressive phenotypes, especially regulatory T (Treg) cells found in the tumor microenvironment. The present study was undertaken to examine whether HS-1793, synthetic resvertrol analog free from the restriction of metabolic instability and high dose requirement of resveratrol, induces an in vivo anti-tumor effect in FM3A tumor bearing mice through the suppression of Treg cells, which contribute to an increase in tumor specific cytotoxic T cell responses. Intraperitoneal injections of HS-1793 showed not only therapeutic benefits on established tumors, but also preventive anti-tumor effects. Treg cells (CD4+CD25+Foxp3+ cells) were significantly reduced in the total splenocytes as well as tumor tissues from HS-1793-administered mice, and the production of TGF-β inducing Treg showed a similar pattern. On the contrary, the administration of HS-1793 increased IFN-γ-expressing CD8+ T cells, upregulated IFN-γ production, and enhanced the cytotoxicity of splenocytes against FM3A tumor cells both in therapeutic and preventive experimental animals. These results demonstrated the suppressive role of HS-1793 on the function of Treg cells contributing to tumor specific cytotoxic T lymphocyte responses in tumor-bearing mice, which explained the underlying mechanism of the anti-tumor immunity of HS-1793.
authors.affiliation: Department of Microbiology, Dong-A University College of Medicine, Busan 602-714, Republic of Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Jeong
authors.forename: Kwang Mo
authors.initials: KM
authors.lastname: Yang
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Choi
authors.forename: Sung Dae
authors.initials: SD
authors.lastname: Kim
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
authors.forename: Su Yeong
authors.initials: SY
authors.lastname: Seo
authors.forename: Sang Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Seong Ryul
authors.initials: SR
authors.lastname: Ryu
authors.forename: Chang Min
authors.initials: CM
authors.lastname: Lee
authors.forename: Hong suk
authors.initials: Hs
authors.lastname: Suh
authors.forename: Wol Soon
authors.initials: WS
authors.lastname: Jo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D009284:Naphthols / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D012118:Resorcinols / Q000494:pharmacology* / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D047368:Tumor Burden / Q000187:drug effects
chemical_list: C523393:4-(6-hydroxy-2-naphthyl)-1,3-benzenediol; D000970:Antineoplastic Agents; D009284:Naphthols; D012118:Resorcinols