title: 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.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To investigate the effect of N. chinensis on differentiation and proliferation in the human promyelocytic leukemic HL-60 cells.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, College of Korean Medicine, Wonkwang University , Iksan, Jeonbuk , Republic of Korea .
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Ju
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.forename: Jun-Gue
authors.initials: JG
authors.lastname: Kang
authors.forename: Sun-Oh
authors.initials: SO
authors.lastname: Jeong
authors.forename: Jang-Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Hyun-Ock
authors.initials: HO
authors.lastname: Pae
authors.forename: Guem-San
authors.initials: GS
authors.lastname: Lee
authors.forename: Won-Sin
authors.initials: WS
authors.lastname: Kim
authors.forename: Yeoung-Su
authors.initials: YS
authors.lastname: Lyu
authors.forename: Byung-Hun
authors.initials: BH
authors.lastname: Jeon
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D016193:G1 Phase / Q000187:drug effects* / Q000502:physiology; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism; D006131:Growth Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism; D032404:Nardostachys; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots; D018547:Plant Stems; D016192:Resting Phase, Cell Cycle / Q000187:drug effects* / Q000502:physiology
chemical_list: C436291:CDKN1B protein, human; D006131:Growth Inhibitors; D010936:Plant Extracts; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Anti-leukemic effect; HL-60 cells; cell-cycle arrest; nardosinone