Liriodenine inhibits the proliferation of human hepatoma cell lines by blocking cell cycle progression and nitric oxide-mediated activation of p53 expression

Food Chem Toxicol. 2005 Jul;43(7):1117-26. doi: 10.1016/j.fct.2005.03.002.


Liriodenine was isolated from the leaves of Michelia compressa. This study was designed to assess cell cycle arrest, the production of nitric oxide (NO) and p53 expression in liriodenine-treated human hepatoma cell lines, including wild-type p53 (Hep G2 and SK-Hep-1). As evidenced by flowcytometric studies, liriodenine induced cell cycle G(1) arrest and inhibited DNA synthesis in Hep G2 and SK-Hep-1 cell lines. The p53, iNOS expression and intracellular NO level were markedly increased in Hep G2 cells after liriodenine treatment. A NO inhibitor, carboxy-PTIO inhibited the p53 expression induced by liriodenine. In addition, liriodenine could not induce obvious cytotoxicity in normal human IMR-90 cell line. These results demonstrate that NO production and p53 expression are critical factors in liriodenine-induced growth inhibition in human wild-type p53 hepatoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Aporphines / chemistry
  • Aporphines / pharmacology*
  • Blotting, Western
  • Bromodeoxyuridine
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle / drug effects*
  • Cell Proliferation / drug effects*
  • Chromatography, Thin Layer
  • DNA, Neoplasm / biosynthesis
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Gene Expression / drug effects
  • Genes, p53 / drug effects*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Magnoliaceae / chemistry
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase Type II
  • Spectrophotometry, Infrared
  • Spectrophotometry, Ultraviolet
  • Tumor Cells, Cultured


  • Antimetabolites
  • Antineoplastic Agents, Phytogenic
  • Aporphines
  • DNA, Neoplasm
  • Nitric Oxide
  • liriodenine
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Bromodeoxyuridine