RRC ID 44311
Author Horlad H, Fujiwara Y, Takemura K, Ohnishi K, Ikeda T, Tsukamoto H, Mizuta H, Nishimura Y, Takeya M, Komohara Y.
Title Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells.
Journal Mol Nutr Food Res
Abstract SCOPE: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.
METHODS AND 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.
CONCLUSION: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.
Volume 57(6)
Pages 1046-54
Published 2013-6-1
DOI 10.1002/mnfr.201200610
PMID 23417831
MeSH Animals Antineoplastic Agents, Phytogenic / pharmacology* Bone Neoplasms / drug therapy* Bone Neoplasms / pathology Cell Line, Tumor / drug effects Cisplatin / pharmacology Doxorubicin / pharmacology Female Humans Immunosuppression Immunosuppressive Agents / pharmacology Lung Neoplasms / drug therapy* Lung Neoplasms / pathology Lung Neoplasms / secondary Lymphocytes / drug effects Lymphocytes / immunology Mice Mice, Inbred C3H Myeloid Cells / drug effects* Myeloid Cells / immunology* Myeloid Cells / pathology Neoplasms, Experimental / drug therapy Osteosarcoma / drug therapy* Osteosarcoma / pathology STAT3 Transcription Factor / metabolism Triterpenes / pharmacology*
IF 4.653
Times Cited 34
Human and Animal Cells