MiR-218-targeting-Bmi-1 mediates the suppressive effect of 1,6,7-trihydroxyxanthone on liver cancer cells

Apoptosis. 2015 Jan;20(1):75-82. doi: 10.1007/s10495-014-1047-3.

Abstract

Traditional Chinese medicine is recently emerged as anti-cancer therapy or adjuvant with reduced side-effects and improved quality of life. In the present study, an active ingredient, 1,6,7-trihydroxyxanthone (THA), derived from Goodyera oblongifolia was found to strongly suppress cell growth and induce apoptosis in liver cancer cells. MicroRNAs are a group of small non-coding RNAs that regulate gene expression at post-transcriptional levels. Our results demonstrated that miR-218 was up-regulated and oncogene Bmi-1 was down-regulated by THA treatment. Further investigation showed that THA-induced-miR-218 up-regulation could lead to activation of tumor suppressor P16(Ink4a) and P14(ARF), the main down-stream targets of Bmi-1. In conclusion, THA might be a potential anti-cancer drug candidate, at least in part, through the activation of miR-218 and suppression of Bmi-1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / therapy
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Orchidaceae / chemistry*
  • Plant Extracts / pharmacology
  • Polycomb Repressive Complex 1 / metabolism*
  • Xanthones / chemistry
  • Xanthones / pharmacology*

Substances

  • 1,6,7-trihydroxyxanthone
  • Antineoplastic Agents
  • BMI1 protein, human
  • MIRN218 microRNA, human
  • MicroRNAs
  • Plant Extracts
  • Xanthones
  • Polycomb Repressive Complex 1