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- W1539482848 abstract "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. We also found that GW9662 attenuated OA‐induced upregulation of C/EBPβ, an important regulator of leukemic differentiation, and p21, which is a potent inhibitor of CDKs that can inhibit phosphorylation of Rb by cyclin D1‐CDK4 complexes. Moreover, our results showed that OA displayed synergistic effects with all‐trans retinoic acid and VD3 in part related to reduction of intranuclear phosphorylated RXRα that has been reported to block nuclear receptor/RXRα heterodimer transcriptional activity. This reduction of phosphorylated RXRα was associated with inhibition of the specific upstream MAP kinase ERK1/2. We suggest that OA may provide a novel complement to AML treatment by its dual effects of augmenting PPARγ activity and sensitizing nuclear receptors to specific ligands." @default.
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- W1539482848 date "2013-09-03" @default.
- W1539482848 modified "2023-10-16" @default.
- W1539482848 title "Oroxylin A has therapeutic potential in acute myelogenous leukemia by dual effects targeting PPARγ and RXRα" @default.
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- W1539482848 doi "https://doi.org/10.1002/ijc.28435" @default.
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