Korean red ginseng extract induces proliferation to differentiation transition of human acute promyelocytic leukemia cells via MYC-SKP2-CDKN1B axis

Title
Korean red ginseng extract induces proliferation to differentiation transition of human acute promyelocytic leukemia cells via MYC-SKP2-CDKN1B axis
Author
조성신
Keywords
Korean red ginseng extract (KRGE); Acute promyelocytic leukemia (APL); Differentiation; CDKN1B; SKP2
Issue Date
2013-09
Publisher
Elsevier Science B.V., Amsterdam.
Citation
Journal of Ethnopharmacology, 2013, 150(2), p.700-707
Abstract
Ethnopharmacological relevance: Korean red ginseng has been used as traditional medicine in East Asia. Recent scientific research revealed multiple effects of Korean red ginseng, including anticancer activity. To evaluate the effect of Korean red ginseng extract (KRGE) in acute promyelocytic leukemia (APL) and elucidate its molecular mechanism.Materials and methods: NB4 cells were treated with 1 mg/ml KRGE for 48 h and examined for cell proliferation and differentiation. Cell cycle distribution of KRGE-treated cells was analyzed and the expression level of G1 phase regulators was determined. MYC was overexpressed by retroviral transduction and its effect on SKP2 and CDKN1B gene expression, cell proliferation, cell cycle and differentiation was evaluated in KRGE-treated cells.Results: KRGE alone was sufficient to induce granulocytic differentiation accompanied with growth inhibition. KRGE treatment resulted in cell cycle arrest at the G1 phase with augmented Cdkn1b proteins without changes in transcript levels. Cycloheximide treatment revealed reduced degradation of Cdkn1b protein by KRGE. In addition, KRGE treatment reduced expression of MYC and SKP2 genes, both at mRNA and protein levels. Upon ectopic expression of MYC, the effect of KRGE was reversed with lesser reduction and induction of SKP2 gene and Cdkn1b protein, respectively. Taken together, these results suggest asequential molecular mechanism from MYC reduction, SKP2 reduction, Cdkn1b protein stabilization, G1 phase arrest to granulocytic differentiation by KRGE in human APL.Conclusions: KRGE induces leukemic proliferation to differentiation transition in APL through modulationof the MYC-SKP2-CDKN1B axis.
URI
https://www.sciencedirect.com/science/article/pii/S0378874113006831?via%3Dihubhttp://hdl.handle.net/20.500.11754/50360
ISSN
0378-8741
DOI
10.1016/j.jep.2013.09.036
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RESEARCH INSTITUTE[S](부설연구소) > ETC
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