4-Acetylantroquinonol B suppresses tumor growth and metastasis of hepatoma cells via blockade of translation-dependent signaling pathway and VEGF production

J Agric Food Chem. 2015 Jan 14;63(1):208-15. doi: 10.1021/jf504434v.

Abstract

Hepatocellular carcinoma (HCC) has become one of most common malignancies and a leading cause of cancer mortality worldwide. Previous study has shown that 4-acetylantroquinonol B (4AAQB) isolated from Antrodia cinnamomea (or niu-chang-chih) was observed to inhibit HepG2 cell proliferation via affecting cell cycle. However, the in vivo effects and antimetastatic activity of 4AAQB have not yet been addressed. This study found that 4AAQB inhibited HepG2 and HuH-7 hepatoma cell growth in both in vitro and in vivo models and exhibited pronounced inhibitory effects on HuH-7 tumor growth in xenograft and orthotopic models. 4AAQB efficiently inhibited the phosphorylation of mTOR and its upstream kinases and the downstream effectors and decreased the production of VEGF and activity of Rho GTPases in HuH-7 cells. Furthermore, 4AAQB inhibited in vitro HuH-7 cell migration and in vivo pulmonary metastasis. The results suggested that 4AAQB is a potential candidate for HCC therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / administration & dosage
  • 4-Butyrolactone / analogs & derivatives*
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antrodia / chemistry*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / physiopathology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Cyclohexanones / administration & dosage*
  • Down-Regulation / drug effects
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / physiopathology
  • Male
  • Metatarsal Bones
  • Mice, Nude
  • Mice, SCID
  • Phosphorylation / drug effects
  • Protein Biosynthesis / drug effects
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Antineoplastic Agents
  • Cyclohexanones
  • Vascular Endothelial Growth Factor A
  • 4-acetylantroquinonol B
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • 4-Butyrolactone