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

Sarathi Hallock, Shou-Ching Tang, L. Maximilian Buja, Benjamin F. Trump, Andrejs Liepins, Priya Weerasinghe

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Sanguinarine, a benzophenanthridine alkaloid, has anticancer potential through induction of cell death. We previously demonstrated that sanguinarine treatment at a low concentration (1.5 μg/ml) induced apoptosis in K562 human erythroleukemia cells, and a high concentration (12.5 μg/ml) induced the morphology of blister formation or oncosis-blister cell death (BCD). Treatment of cells at an intermediate sanguinarine concentration (6.25 μg/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.

Original languageEnglish (US)
Pages (from-to)300-309
Number of pages10
JournalToxicologic Pathology
Volume35
Issue number2
DOIs
Publication statusPublished - Mar 12 2007

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Keywords

  • Apoptosis
  • Aurintricarboxylic acid
  • Bimodal cell death
  • Cycloheximide
  • Necrosis
  • Oncosis
  • Sanguinarine

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology

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