Nardostachys chinensis induces granulocytic differentiation with the suppression of cell growth through p27(Kip1) protein-related G0/G1 phase arrest in human promyelocytic leukemic cells

• Published in: Pharmaceutical biology Vol. 53; no. 7; p. 1002
• Main Authors: Ju, Sung-Min, Lee, Jun, Kang, Jun-Gue, Jeong, Sun-Oh, Park, Jang-Ho, Pae, Hyun-Ock, Lee, Guem-San, Kim, Won-Sin, Lyu, Yeoung-Su, Jeon, Byung-Hun
• Format: Journal Article
• Language: English
• Published: England 01-07-2015
• Subjects: Cell Differentiation - drug effects; Cell Differentiation - physiology; Cyclin-Dependent Kinase Inhibitor p27 - biosynthesis; G1 Phase - drug effects; G1 Phase - physiology; Granulocytes - drug effects; Granulocytes - metabolism; Growth Inhibitors - isolation & purification; Growth Inhibitors - pharmacology; HL-60 Cells; Humans; Leukemia, Promyelocytic, Acute - metabolism; Nardostachys; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Roots; Plant Stems; Resting Phase, Cell Cycle - drug effects; Resting Phase, Cell Cycle - physiology; cell-cycle arrest; Anti-leukemic effect; HL-60 cells; nardosinone
• ISSN: 1744-5116
• DOI: 10.3109/13880209.2014.952834

Nardostachys chinensis Batalin (Valerianaceae) has been used in Korean traditional medicine to elicit stomachic and sedative effects. However, the anti-leukemic activities of N. chinensis have not been well examined.
To investigate the effect of N. chinensis on differentiation and proliferation in the human promyelocytic leukemic HL-60 cells.
The dried roots and stems of N. chiensis are extracted using hot water and then freeze-dried. The yield of extract was 12.82% (w/w). The HL-60 cells were treated with 25-200 μg/ml of N. chinensis for 72 h or 100 μg/ml of N. chinensis for 24-72 h.
Nardostachys chinensis significantly inhibited cell viability dose dependently with an IC50 of 100 μg/ml in HL-60 cells. Nardostachys chinensis induced differentiation of the cells as measured by reduction activity of NBT and expression of CD11b but not of CD14 as analyzed by flow cytometry, which indicates a differentiation toward the granulocytic lineage. Nardostachys chinensis also induced growth inhibition through G0/G1 phase arrest in the cell cycle of HL-60 cells. Among the G0/G1 phase in the cell cycle-related protein, the expression of cyclin-dependent kinase (CDK) inhibitor p27(Kip1) was increased in N. chinensis-treated HL-60 cells, whereas the expression levels of CDK2, CDK4, CDK6, cyclin D1, cyclin D3, cyclin E, and cyclin A were decreased. Interestingly, N. chinensis markedly enhanced the binding of p27(Kip1) with CDK2 and CDK6.
This study demonstrated that N. chinensis is capable of inducing cellular differentiation and growth inhibition through p27(Kip1) protein-related G0/G1 phase arrest in HL-60 cells.