title: Oleanolic acid inhibits macrophage differentiation into the M2 phenotype             and glioblastoma cell proliferation by suppressing the activation of STAT3.
abstract: Tumor-associated macrophages (TAMs) polarized to the M2 phenotype promote             tumor cell proliferation and are associated with a poor prognosis in patients             with high grade glioma. We previously revealed that corosolic acid, a triterpenoid             compound, inhibits the M2 polarization of human monocyte-derived macrophages (HMDM).             In the present study, we examined whether oleanolic acid (OA), a triterpenoid             compound whose structure is similar to corosolic acid, also shows inhibitory effects             on M2 polarization in HMDM. OA significantly inhibited the expression of CD163,             one of the phenotype markers of M2 macrophages, as well as suppressed the secretion             of IL-10, one of the anti-inflammatory cytokines preferentially produced by M2             macrophages, thus suggesting that OA suppresses the M2 polarization of macrophages.             Furthermore, OA inhibited the proliferation of U373 human glioblastoma cells,             and the activation of signal transducer and activator of transcription-3 (STAT3)             in both human macrophages and glioblastoma cells. These results indicate that             OA suppresses the M2 polarization of macrophages and tumor cell proliferation             by inhibiting STAT3 activation. Therefore, OA may be a potentially new agent that             can be used for the prevention and treatment of various malignant tumors, including             glioma.
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
authors.forename: Rino
authors.initials: R
authors.lastname: Kudo
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Tsurushima
authors.forename: Koji
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D016764:Cell Polarity; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival; D005909:Glioblastoma; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D009828:Oleanolic Acid / Q000494:pharmacology*; D010641:Phenotype; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10; D018664:Interleukin-12; D009828:Oleanolic Acid; C507924:JAK2 protein, human; D053614:Janus Kinase 2