Berberine enhances the radiosensitivity of hepatoma cells by Nrf2 pathway

Front Biosci (Landmark Ed). 2019 Jun 1;24:1190-1202.

Abstract

Radiation therapy is a major treatment in hepatocellular carcinoma (HCC). Yet, this treatment is ineffective in HCC due to lack of radiosensitivity. For this reason, we examined whether berberine (BBR) might modify the radioresistance of HCC cells. BBR enhances the radiation-induced oxidative stress and apoptosis in Huh7 and HepG2 cells while it protectes HHL-5 cells from radiation damage. To test the importance of Nrf2, a master transcription factor in oxidative damage, the effect of BBR is studied in irradiated Nrf2-deficient cells. BBR fails to induce the radiosensitivity in Nrf2-deficient cells suggesting that Nrf2 is required for the effect of BBR. BBR suppresses the expression of Nrf2 signaling-related proteins (Nrf2, HO-1 and NQO-1) in Huh7 and HepG2 cells, demonstrating that BBR strengthens radiosensitivity via suppressing Nrf2 signaling pathway in HCC cells. Furthermore, experiment using xenografts in nude mice indicated that BBR enhances the growth inhibitory effect of radiation in a Nrf2-dependent manner in vivo. In conclusion, these results suggest that BBR is a promising potential sensitizer for the radiotherapy of HCC.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Berberine / pharmacology*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / radiotherapy
  • Cell Line
  • Cell Line, Tumor
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / radiotherapy
  • Mice, Inbred BALB C
  • Mice, Nude
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • RNA Interference
  • Radiation Tolerance / drug effects*
  • Radiation Tolerance / genetics
  • Radiation Tolerance / radiation effects
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / radiation effects
  • Xenograft Model Antitumor Assays*

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Berberine