Induction of Egr-1 is associated with anti-metastatic and anti-invasive ability of beta-lapachone in human hepatocarcinoma cells

Biosci Biotechnol Biochem. 2007 Sep;71(9):2169-76. doi: 10.1271/bbb.70103. Epub 2007 Sep 7.


beta-lapachone, a quinone compound obtained from the bark of the lapacho tree (Tabebuia avellanedae), was reported to have anti-inflammatory and anti-cancer activities. In this study, we investigated novel functions of beta-lapachone in terms of anti-metastasis and anti-invasion abilities using human hepatocarcinoma cell lines, HepG2 and Hep3B. beta-lapachone dose-dependently inhibited cell viability and migration of both HepG2 and Hep3B cells, as determined by methylthiazoletetrazolium (MTT) assay and wound healing assay. RT-PCR and Western blot data revealed that beta-lapachone dramatically increased the levels of protein, as well as mRNA expression of early growth response gene-1 (Egr-1) and throbospondin-1 (TSP-1) at an early point in time, and then decreased in a time-dependent manner. In addition, down-regulation of Snail and up-regulation of E-cadherin expression were observed in beta-lapachone-treated HepG2 and Hep3B cells, and this the associated with decreased invasive ability as measured by matrigel invasion assay. Taken together, our results strongly suggest that beta-lapachone may be expected to inhibit the progression and metastasis of hepatoma cells, at least in part by inhibiting the invasive ability of the cells via up-regulation of the expression of the Egr-1, TSP-1, and E-cadherin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / metabolism
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Naphthoquinones / pharmacology*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / pathology
  • Snail Family Transcription Factors
  • Thrombospondin 1 / genetics
  • Thrombospondin 1 / metabolism
  • Transcription Factors / metabolism


  • Cadherins
  • Early Growth Response Protein 1
  • Naphthoquinones
  • Snail Family Transcription Factors
  • Thrombospondin 1
  • Transcription Factors
  • beta-lapachone