Aurintricarboxylic acid inhibits protein synthesis independent, sanguinarine-induced apoptosis and oncosis

Toxicol Pathol. 2007 Feb;35(2):300-9. doi: 10.1080/01926230701194211.


Sanguinarine, a benzophenanthridine alkaloid, has anticancer potential through induction of cell death. We previously demonstrated that sanguinarine treatment at a low concentration (1.5 microg/ml) induced apoptosis in K562 human erythroleukemia cells, and a high concentration (12.5 microg/ml) induced the morphology of blister formation or oncosis-blister cell death (BCD). Treatment of cells at an intermediate sanguinarine concentration (6.25 microg/ml) induced diffuse swelling or oncosis-diffuse cell swelling (DCS). To assess the underlying mechanism of sanguinarine-induced apoptosis and oncosis-BCD in K562 cells, we studied their response to pre-treatment with two chemical compounds: aurintricarboxylic acid (ATA) and cycloheximide (CHX). The pretreatment effects of both chemical compounds on apoptosis and oncosis-BCD were evaluated by measuring multiple parameters using quantitative morphology, electron microscopy, terminal deoxynucleotidyl transferase (TdT) end-labeling and annexin-V-binding. ATA, a DNA endonuclease inhibitor, efficiently prevented DNA nicking and inhibited apoptosis almost completely and oncosis-BCD by about 40%, while CHX, a protein synthesis inhibitor, failed to inhibit both apoptosis and oncosis-BCD. These results demonstrate, first, the importance of endonuclease in sanguinarine-induced apoptosis and to some extent in oncosis-BCD and, second, that this inhibition does not require de novo protein synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Aurintricarboxylic Acid / pharmacology*
  • Benzophenanthridines / pharmacology*
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / drug effects*
  • Cycloheximide / pharmacology
  • Deoxyribonuclease I / antagonists & inhibitors
  • Deoxyribonuclease I / physiology
  • Dose-Response Relationship, Drug
  • Humans
  • Isoquinolines / pharmacology*
  • Leukemia, Erythroblastic, Acute / pathology
  • Leukemia, Erythroblastic, Acute / physiopathology
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / physiology
  • Protein Synthesis Inhibitors / pharmacology*


  • Alkaloids
  • Antineoplastic Agents
  • Benzophenanthridines
  • Isoquinolines
  • Protein Synthesis Inhibitors
  • Aurintricarboxylic Acid
  • Cycloheximide
  • sanguinarine
  • Deoxyribonuclease I