The adjuvant effects of Antrodia Camphorata extracts combined with anti-tumor agents on multidrug resistant human hepatoma cells

J Ethnopharmacol. 2008 Aug 13;118(3):387-95. doi: 10.1016/j.jep.2008.05.001. Epub 2008 May 7.

Abstract

Aim of the study: The objectives of this study were to investigate the adjuvant anti-tumor effects of Antrodia camphorate in human hepatoma cells (C3A and PLC/PRF/5) which are resistance to most anti-tumor agents, elucidate the possible regulation pathways, and measure the tumor growth and survival rate in xenograft-nude mice after combined with anti-tumor agents.

Materials and methods: The AC extracts were measured by using a phenol/sulfuric acid method as previously described. The in vitro cell proliferation assay of ACs and anti-tumor agents was tested on C3A and PLC/PRF/5 cell lines. The percentage of human hepatoma cells undergoing apoptosis and distributing in different phases of cell cycle were determined by Flow cytometric analysis. Western blot analysis for MDR-1 and apoptosis- related proteins. The measurements of tumor growth and survival analysis of hepatoma implanted nude mice treated with Antrodia camphorata extracts and anti-tumor agents alone or in combinations.

Results: We have found that Antrodia camphorata extracts, when combined with anti-tumor agents, showed adjuvant antiproliferative effects on hepatoma cells (in vitro) and on xenografted cells in tumor-implanted nude mice (in vivo), which then extended their median survival days. Furthermore, solid-state extracts of Antrodia camphorata (AC-SS) showed its adjuvant effects through the inhibition of MDR gene expressions and the pathway of COX-2- dependent inhibition of p-AKT, which ultimately resulted in the induction of apoptosis in hepatoma cells.

Conclusions: In this study, we have found that Antrodia camphorata extract, when combined with anti-tumor agents, showed adjuvant antiproliferative effects on hepatoma cells (in vitro) and on xenografted cells in tumor-implanted nude mice (in vivo).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cyclooxygenase 2 / analysis
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Mice
  • Mice, Inbred ICR
  • Phytotherapy*
  • Plant Extracts / administration & dosage*
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / analysis

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Plant Extracts
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases