Antioxidant xanthone derivatives induce cell cycle arrest and apoptosis and enhance cell death induced by cisplatin in NTUB1 cells associated with ROS

Eur J Med Chem. 2011 Apr;46(4):1222-31. doi: 10.1016/j.ejmech.2011.01.043. Epub 2011 Feb 4.

Abstract

In an effort to develop novel antioxidant as anticancer agents, a series of xanthones were prepared. In vitro screening, the synthetic xanthones revealed significant inhibitory effects on xanthine oxidase and ABTS radical-cation scavenging activity. The selective compounds 2 and 8 induced an accumulation of NTUB1 cells in the G(1) phase arrest and cellular apoptosis by the increase of ROS level. The combination of cisplatin and 2 significantly enhanced the cell death in NTUB1 cells. Compounds 2 and 8 did not show cytotoxic activity in selected concentrations against SV-HUC1 cells. The present results suggested that antioxidants 2 and 8 may be used as anticancer agent for enhancing the therapeutic efficacy of anticancer agents and to reduce their side effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • DNA Breaks / drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Drug Synergism
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • Humans
  • Reactive Oxygen Species / metabolism*
  • Structure-Activity Relationship
  • Xanthones / chemical synthesis
  • Xanthones / chemistry*
  • Xanthones / pharmacology*

Substances

  • Antineoplastic Agents
  • Free Radical Scavengers
  • Reactive Oxygen Species
  • Xanthones
  • xanthone
  • Cisplatin