Oroxylin A (OA) is a flavonoid derived from a Chinese herb that has previously been reported to inhibit the proliferation of several cancer cell lines. It is found that OA significantly inhibited the growth of myeloid leukemia cell lines and as xenografts in immunodeficient mice and primary blasts from acute myelogenous leukemia (AML) patients. Furthermore, OA-induced cell cycle arrest and differentiation were observed in OA-treated AML cell lines. OA-induced increase of CD11b/CD14 expression was reversed by GW9662, a specific PPARγ inhibitor, or transient transfection with PPARγ siRNA. Docking study showed OA bound to ligand-binding domain of PPARγ via forming hydrogen bonds with Arg288 and Leu340 sites. Results of fluorescence polarization-based ligand assay verified PPARγ-binding activity of OA, and in OA-treated cells, intranuclear accumulation and increased binding activity of PPARγ to PPRE were detected.
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