title: Onionin A, a sulfur-containing compound isolated from onions, impairs tumor development and lung metastasis by inhibiting the protumoral and immunosuppressive functions of myeloid cells.
abstract: Recent studies have demonstrated that myeloid lineage cells, such as macrophages and myeloid suppressor cells (MDSCs), are major components exhibiting protumoral functions in the setting of tumor progression. Tumor-associated macrophages polarized to the protumoral M2 phenotype promote tumor proliferation and are considered to be a therapeutic target in patients with malignant tumors.
  
  
  
  We identified a new candidate compound, called onionin A (ONA) isolated from onions, that inhibits macrophage polarization into the M2 phenotype, as well as the immunosuppressive activity of MDSCs and tumor proliferation, by suppressing signal transducer and activator of transcription-3 (Stat3) activation. Furthermore, ONA administration was found to significantly suppress subcutaneous tumor development and lung metastasis in tumor-bearing mice. ONA administration also inhibited Stat3 activation and increased the number of infiltrating lymphocytes in tumor tissues, and an ex vivo analysis showed that the immunosuppressive effect of MDSCs in tumor-bearing mice is impaired by ONA. Moreover, ONA regulated tumor proliferation by inhibiting cell-cell interactions between macrophages and tumor cells, and ONA administration enhanced the antitumor effects of cisplatin in the tumor-bearing mice.
  
  
  
  These findings demonstrate that ONA may be a potential new tool for antitumor therapy and also for tumor prevention.
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hasita
authors.initials: H
authors.lastname: Horlad
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shiraishi
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Tsuboki
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Rino
authors.initials: R
authors.lastname: Kudo
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nohara
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects*; D019697:Onions / Q000737:chemistry*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013454:Sulfoxides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013455:Sulfur / Q000737:chemistry*; D013876:Thiophenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D007166:Immunosuppressive Agents; D050796:STAT3 Transcription Factor; D013454:Sulfoxides; D013876:Thiophenes; C551608:onionin A; D013455:Sulfur; D002945:Cisplatin
keywords: MDSCs; Macrophages; Onionin A; Stat3; Tumor cells