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Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid‐derived suppressor cells
Author(s) -
Horlad Hasita,
Fujiwara Yukio,
Takemura Kenichi,
Ohnishi Koji,
Ikeda Tsuyoshi,
Tsukamoto Hirotake,
Mizuta Hiroshi,
Nishimura Yasuharu,
Takeya Motohiro,
Komohara Yoshihiro
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200610
Subject(s) - cancer research , stat3 , myeloid derived suppressor cell , stat protein , immunosuppression , metastasis , in vivo , systemic administration , medicine , immune system , lewis lung carcinoma , immunology , chemistry , pharmacology , cancer , biology , suppressor , signal transduction , biochemistry , microbiology and biotechnology
Scope Recent studies demonstrated that myeloid cells are associated with systemic immunosuppression in tumor‐bearing hosts. In particular, myeloid cells positive for G r‐1 and CD 11b 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 ( S tat3) 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 m RNA expressions of cyclooxygenase‐2 and CCL 2 in MDSC were significantly decreased by CA administration. Furthermore, CA enhanced the antitumor effects of adriamycin and cisplatin in in vitro. Conclusion Since S tat3 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.