Department of Biomedical Science, Graduate School of Biomedical Science and Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Republic of Korea; Hanyang Biomedical Research Institute, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Republic of Korea.
J Ethnopharmacol. 2013 Nov 25;150(2):700-7. doi: 10.1016/j.jep.2013.09.036. Epub 2013 Oct 2.
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.
NB4 cells were treated with 1mg/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.
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 a sequential molecular mechanism from MYC reduction, SKP2 reduction, Cdkn1b protein stabilization, G1 phase arrest to granulocytic differentiation by KRGE in human APL.
KRGE induces leukemic proliferation to differentiation transition in APL through modulation of the MYC-SKP2-CDKN1B axis.
韩国红参已在东亚被用作传统药物。最近的科学研究揭示了韩国红参的多种作用，包括抗癌活性。为了评估韩国红参提取物（KRGE）在急性早幼粒细胞白血病（APL）中的作用，并阐明其分子机制。
将 NB4 细胞用 1mg/ml KRGE 处理 48 小时，检测细胞增殖和分化。分析 KRGE 处理细胞的细胞周期分布，并测定 G1 期调节因子的表达水平。通过逆转录病毒转导过表达 MYC，并评估其对 SKP2 和 CDKN1B 基因表达、细胞增殖、细胞周期和分化的影响在 KRGE 处理的细胞中。
KRGE 单独足以诱导粒细胞分化并伴有生长抑制。KRGE 处理导致细胞周期停滞在 G1 期，Cdkn1b 蛋白增加而转录水平不变。环磷酰胺处理显示 KRGE 减少了 Cdkn1b 蛋白的降解。此外，KRGE 处理降低了 MYC 和 SKP2 基因的表达，无论是在 mRNA 还是蛋白质水平。MYC 异位表达时，KRGE 的作用被逆转，SKP2 基因和 Cdkn1b 蛋白的减少和诱导分别减少。总之，这些结果表明，KRGE 通过调节 MYC-SKP2-CDKN1B 轴，在人 APL 中诱导白血病增殖向分化转变。
KRGE 通过调节 MYC-SKP2-CDKN1B 轴，诱导 APL 中的白血病增殖向分化转变。
