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 language | English (US) |
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Pages (from-to) | 300-309 |
Number of pages | 10 |
Journal | Toxicologic Pathology |
Volume | 35 |
Issue number | 2 |
DOIs | |
State | Published - Mar 12 2007 |
Externally published | Yes |
Keywords
- Apoptosis
- Aurintricarboxylic acid
- Bimodal cell death
- Cycloheximide
- Necrosis
- Oncosis
- Sanguinarine
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Molecular Biology
- Toxicology
- Cell Biology