title: Vitamin K2 inhibits the proliferation of HepG2 cells by up-regulating the transcription of p21 gene.
abstract: OBJECTIVE
  Vitamin K2 has been reported to inhibit the growth of human hepatocellular carcinoma (HCC) in vitro and suppress hepatocarcinogenesis in vivo. However, its inhibitory mechanism has not yet been clarified.
  
  
  METHODS
  Different concentrations of vitamin K2 (30, 10, 1, 0.1 and 0.01 muM) were added to the HCC cell line HepG2 to assess effects on cell growth. The effect of vitamin K2 on cell cycle progression was determined by flow-cytometric analysis. The expression of cell cycle regulatory proteins p21 and p27 was then examined by Western blot. Whether vitamin K2 regulates the gene expression through action on the p21 promoter region was investigated by luciferase assay.
  
  
  RESULTS
  Vitamin K2 inhibited the growth of HepG2 cells dose-dependently, and its inhibitory rate reached approximately 50% at the dose of 30 muM after 96 h treatment. After treatment with vitamin K2, the proportion of cells in G0-G1 phase increased, and in S phase decreased. Apoptotic cells were not detected. The expression of cell cycle regulatory protein p21 was induced by vitamin K2 treatment, but p27 was not. By the luciferase assay, vitamin K2 significantly activated the promoter of p21. Knock-down of p21 by siRNA reversed the growth inhibition of HepG2 cells by vitamin K2.
  
  
  CONCLUSIONS
  The findings suggest that vitamin K2 suppresses the proliferation of HCC cells by blocking the cell cycle G1/S progression through the transcriptional induction of p21.
authors: Division of Hepatobiliary and Pancreatic Medicine, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
authors: Weidong
authors: W
authors: Liu
authors: Hideji
authors: H
authors: Nakamura
authors: Teruhisa
authors: T
authors: Yamamoto
authors: Naoto
authors: N
authors: Ikeda
authors: Masaki
authors: M
authors: Saito
authors: Masao
authors: M
authors: Ohno
authors: Naoki
authors: N
authors: Hara
authors: Hiroyasu
authors: H
authors: Imanishi
authors: Soji
authors: S
authors: Shimomura
authors: Tetsuo
authors: T
authors: Yamamoto
authors: Toshiyuki
authors: T
authors: Sakai
authors: Shuhei
authors: S
authors: Nishiguchi
authors: Toshikazu
authors: T
authors: Hada