1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate induced autophagic cell death in human PC3 cells

Chem Biol Interact. 2018 Feb 1;281:60-68. doi: 10.1016/j.cbi.2017.12.010. Epub 2017 Dec 19.

Abstract

The autophagy of human prostate cancer cells (PC3 cells) induced by a new anthraquinone derivative, 1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate (PA) was investigated, and the relationship between autophagy and reactive oxygen species (ROS) generation was studied. The results indicated that PA induced PC3 cell death in a time- and dose-dependent manner, could inhibit PC3 cell growth by G1 phase cell cycle arrest and corresponding decrease in the G2/M cell population and induced S-phase arrest accompanied by a significant decrease G2/M and G1 phase numbers after PC3 cells treated with PA for 48 h, and increased the accumulation of autophagolysosomes and microtubule-associated protein LC3-ll, a marker of autophagy. However, these phenomenon were not observed in the group pretreated with the autophagy inhibitor 3-MA or Bafilomycin A1 (BAF), suggesting that PA induced PC3 cell autophagy. In addition, we found that PA triggered ROS generation in cells, while the levels of ROS decreased in the N-acetylcysteine (NAC) co-treatment, indicating that PA-mediated autophagy was partly blocked by NAC. In summary, the autophagic cell death of human PC3 cells mediated by PA-triggered ROS generation.

Keywords: Anthraquinone derivatives; Autophagy; Prostate cancer; ROS.

MeSH terms

  • Acetylcysteine / pharmacology
  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Anthraquinones / chemical synthesis
  • Anthraquinones / chemistry
  • Anthraquinones / toxicity*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Macrolides / pharmacology
  • Microscopy, Electron, Transmission
  • Microtubule-Associated Proteins / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Anthraquinones
  • MAP1LC3A protein, human
  • Macrolides
  • Microtubule-Associated Proteins
  • Reactive Oxygen Species
  • 3-methyladenine
  • bafilomycin A1
  • Caspase 3
  • Adenine
  • Acetylcysteine