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Oncol Rep. 2011 Dec;26(6):1533-7. doi: 10.3892/or.2011.1454. Epub 2011 Sep 12.

Oleanolic acid inhibits macrophage differentiation into the M2 phenotype and glioblastoma cell proliferation by suppressing the activation of STAT3.

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


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.

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