期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 65, 期 35, 页码 7687-7697出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.7b02299
关键词
ginsenoside; immediate-early gene; apoptosis; myeloid differentiation; hematologic malignancy
资金
- NSFC Projects [81373903, 81202946]
- Chongqing Research Program of Basic Research and Frontier Technology [cstc2017jcy-jAX0299]
- TCM Project of Chongqing Health and Family Planning Commission [ZY201702120]
- Key Project of Fundamental Research Fund for the Central Universities [XDJK2016B040, XDJK2016B034]
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, DRS, 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 DRS 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.
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