title: A novel strategy for inducing the antitumor effects of triterpenoid compounds: blocking the protumoral functions of tumor-associated macrophages via STAT3 inhibition.
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.
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Yukio
authors.identifier: 0000-0002-2074-0597
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Motohiro
authors.identifier: 0000-0003-3694-1294
authors.initials: M
authors.lastname: Takeya
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009828:Oleanolic Acid / Q000494:pharmacology / Q000627:therapeutic use; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor; D014315:Triterpenes; D009828:Oleanolic Acid; C113861:corosolic acid
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