First two authors have equally contributed to this work.
Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells
Article first published online: 18 FEB 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Special Issue: Cocoa and Human Health
Volume 57, Issue 6, pages 1046–1054, June 2013
How to Cite
Horlad, H., Fujiwara, Y., Takemura, K., Ohnishi, K., Ikeda, T., Tsukamoto, H., Mizuta, H., Nishimura, Y., Takeya, M. and Komohara, Y. (2013), Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells. Mol. Nutr. Food Res., 57: 1046–1054. doi: 10.1002/mnfr.201200610
- Issue published online: 7 JUN 2013
- Article first published online: 18 FEB 2013
- Manuscript Accepted: 21 DEC 2012
- Manuscript Revised: 2 DEC 2012
- Manuscript Received: 14 SEP 2012
- Ministry of Education, Culture, Sports, Science, and Technology of Japan. Grant Numbers: 20390113, 21790388, 23790747
- Corosolic acid;
- Lung metastasis;
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.
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.