Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells.

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.

• Authors: Hasita Horlad, Yukio Fujiwara, Kenichi Takemura, Koji Ohnishi, Tsuyoshi Ikeda, Hirotake Tsukamoto, Hiroshi Mizuta, Yasuharu Nishimura, Motohiro Takeya, Yoshihiro Komohara
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 57 Issue 6 Pg. 1046-54 (Jun 2013) ISSN: 1613-4133 [Electronic] Germany
• PMID: 23417831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antineoplastic Agents, Phytogenic
• Immunosuppressive Agents
• STAT3 Transcription Factor
• Triterpenes
• Doxorubicin
• corosolic acid
• Cisplatin

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Bone Neoplasms (drug therapy, pathology)
• Cell Line, Tumor (drug effects)
• Cisplatin (pharmacology)
• Doxorubicin (pharmacology)
• Female
• Humans
• Immunosuppression Therapy
• Immunosuppressive Agents (pharmacology)
• Lung Neoplasms (drug therapy, pathology, secondary)
• Lymphocytes (drug effects, immunology)
• Mice
• Mice, Inbred C3H
• Myeloid Cells (drug effects, immunology, pathology)
• Neoplasms, Experimental (drug therapy)
• Osteosarcoma (drug therapy, pathology)
• STAT3 Transcription Factor (metabolism)
• Triterpenes (pharmacology)