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BioMed Research International
Volume 2014 (2014), Article ID 348539, 11 pages
http://dx.doi.org/10.1155/2014/348539
Review Article

A Novel Strategy for Inducing the Antitumor Effects of Triterpenoid Compounds: Blocking the Protumoral Functions of Tumor-Associated Macrophages via STAT3 Inhibition

Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan

Received 1 January 2014; Accepted 4 February 2014; Published 11 March 2014

Academic Editor: Masahisa Jinushi

Copyright © 2014 Yukio Fujiwara et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

There are many types of nontumor cells, including leukocytes, fibroblasts, and endothelial cells, in the tumor microenvironment. Among these cells, infiltrating macrophages have recently received attention as novel target cells due to their protumoral functions. Infiltrating macrophages are called tumor-associated macrophages (TAMs). TAMs polarized to the M2 phenotype are involved in tumor development and are associated with a poor clinical prognosis. Therefore, the regulation of TAM activation or M2 polarization is a new strategy for antitumor therapy. We screened natural compounds possessing an inhibitory effect on the M2 polarization of human macrophages. Among 200 purified natural compounds examined, corosolic acid (CA) and oleanolic acid (OA), both are categorized in triterpenoid compounds, inhibited macrophage polarization to M2 phenotype by suppressing STAT3 activation. CA and OA also directly inhibited tumor cell proliferation and sensitized tumor cells to anticancer drugs, such as adriamycin and cisplatin. The in vivo experiments showed that CA significantly suppressed subcutaneous tumor development and lung metastasis in a murine sarcoma model. The application of triterpenoid compounds, such as CA and OA, is a potential new anticancer therapy targeting macrophage activation, with synergistic effects with anticancer agents.