Liquiritigenin exhibits antitumour action in pituitary adenoma cells via Ras/ERKs and ROS-dependent mitochondrial signalling pathways

J Pharm Pharmacol. 2014 Mar;66(3):408-17. doi: 10.1111/jphp.12170. Epub 2013 Nov 6.

Abstract

Objective: The purpose of this study was to investigate antitumour effects of liquiritigenin (LQ) on pituitary adenoma in in-vitro and in-vivo models.

Methods: The effects of LQ on cell viability, apoptosis rate, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) level and various apoptosis-related mediators were examined in MMQ and GH3 cells that are derived from rat pituitary adenoma. Antitumour effect of LQ was also examined in the mouse model of GH3-xenografted tumour.

Key findings: LQ inhibited cell viability, caused G1 phase arrest and initiated apoptosis in both MMQ and GH3 cells. LQ dissipated MMP, increased intracellular ROS level and cytosol cytochrome C, and reduced the expression of Ras, B-cell lymphoma 2 and B-cell lymphoma-extra large. LQ also inhibited the activation of extracellular signalling-regulated kinases (ERKs) and the translocation of from cytoplasm to nucleus. LQ markedly reduced tumour size without affecting bodyweight in mice with GH3 cells xenograft.

Conclusions: LQ effectively inhibits pituitary adenoma tumour growth and induces cell apoptotic death mainly via Ras/ERKs and ROS-dependent mitochondrial pathways, suggesting that LQ is a potential suppressor of pituitary adenoma.

Keywords: ROS; Ras/ERKs; apoptosis; liquiritigenin; pituitary adenoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Biological Transport
  • Cytochromes c / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flavanones / pharmacology
  • Flavanones / therapeutic use*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phytotherapy*
  • Pituitary Neoplasms / drug therapy*
  • Pituitary Neoplasms / metabolism
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Flavanones
  • Plant Extracts
  • Reactive Oxygen Species
  • Cytochromes c
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinases
  • liquiritigenin