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Ginsenoside 20(S)-Rh2 Induces Apoptosis and Differentiation of Acute Myeloid Leukemia Cells: Role of Orphan Nuclear Receptor Nur77

Author:
Wang, Chengqiang, He, Hui, Dou, Guojun, Li, Juan, Zhang, Xiaomei, Jiang, Mingdong, Li, Pan, Huang, Xiaobo, Chen, Hongxi, Li, Li, Yang, Dajian, Qi, Hongyi
Source:
Journal of agricultural and food chemistry 2017 v.65 no.35 pp. 7687-7697
ISSN:
1520-5118
Subject:
apoptosis, caspase-3, caspase-8, caudal vein, death domain receptors, flow cytometry, mice, mitochondria, myeloid leukemia, neoplasm cells, severe combined immunodeficiency, signal transduction, staining
Abstract:
Ginsenoside 20(S)-Rh2 has been shown to induce apoptosis and differentiation of acute myeloid leukemia (AML) cells. However, the underlying molecular mechanisms are not fully understood. In our study, 20(S)-Rh2 induced the expression of orphan nuclear receptor Nur77 and death receptor proteins Fas, FasL, DR5, and TRAIL, as well as the cleavage of caspase 8 and caspase 3 in HL-60 cells. Importantly, shNur77 attenuated 20(S)-Rh2-induced apoptosis and Fas and DR5 expression. Meanwhile, 20(S)-Rh2 promoted Nur77 translocation from the nucleus to mitochondria and enhanced the interaction between Nur77 and Bcl-2, resulting in the exposure of the BH3 domain of Bcl-2 and activation of Bax. Furthermore, 20(S)-Rh2 promoted the differentiation of HL-60 cells as evidenced by Wright-Giemsa staining, NBT reduction assay, and detection of the myeloid differentiation marker CD11b by flow cytometry. Notably, shNur77 reversed 20(S)-Rh2-mediated HL-60 differentiation. Additionally, 20(S)-Rh2 also exhibited an antileukemic effect and induced Nur77 expression in NOD/SCID mice with the injection of HL-60 cells into the tail vein. Together, our studies suggest that the Nur77-mediated signaling pathway is highly involved in 20(S)-Rh2-induced apoptosis and differentiation of AML cells.
Agid:
5799827