title: Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells.
abstract: METHODS
  Recent studies demonstrated that myeloid cells are associated with systemic immunosuppression in tumor-bearing hosts. In particular, myeloid cells positive for Gr-1 and CD11b in tumor-bearing mice are called myeloid-derived suppressor cells (MDSC) because of their suppression of T-cell activation. In this study, we investigated the antitumor effects of corosolic acid (CA) in murine sarcoma model.
  
  
  RESULTS
  The results from the in vivo study showed that CA administration did not suppress the tumor proliferation index, but significantly impaired subcutaneous tumor development and lung metastasis. Furthermore, CA administration inhibited signal transducer and activator of transcription-3 (Stat3) activation and increased in the number of infiltrating lymphocytes in tumor tissues. Ex vivo analysis demonstrated that a significant immunosuppressive effect of MDSC in tumor-bearing mice was abrogated and the mRNA expressions of cyclooxygenase-2 and CCL2 in MDSC were significantly decreased by CA administration. Furthermore, CA enhanced the antitumor effects of adriamycin and cisplatin in in vitro.
  
  
  CONCLUSIONS
  Since Stat3 is associated with tumor progression not only in osteosarcoma, but also in other malignant tumors, our findings indicate that CA might be widely useful in anticancer therapy by targeting the immunosuppressive activity of MDSC and through its synergistic effects with anticancer agents.
authors: Department of Cell Pathology, Faculty of Medical and Pharmaceutical Sciences, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Hasita
authors: H
authors: Horlad
authors: Yukio
authors: Y
authors: Fujiwara
authors: Kenichi
authors: K
authors: Takemura
authors: Koji
authors: K
authors: Ohnishi
authors: Tsuyoshi
authors: T
authors: Ikeda
authors: Hirotake
authors: H
authors: Tsukamoto
authors: Hiroshi
authors: H
authors: Mizuta
authors: Yasuharu
authors: Y
authors: Nishimura
authors: Motohiro
authors: M
authors: Takeya
authors: Yoshihiro
authors: Y
authors: Komohara
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007166:Immunosuppressive Agents; D050796:STAT3 Transcription Factor; D014315:Triterpenes; D004317:Doxorubicin; C113861:corosolic acid; D002945:Cisplatin