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 Citations (Scopus)

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
StatePublished - Mar 12 2007

Fingerprint

Aurintricarboxylic Acid
Cell death
Blister
Cell Death
Apoptosis
Proteins
Chemical compounds
Cycloheximide
Swelling
Benzophenanthridines
Leukemia, Erythroblastic, Acute
Protein Synthesis Inhibitors
K562 Cells
DNA Nucleotidylexotransferase
Endonucleases
Annexin A5
Deoxyribonuclease I
sanguinarine
Alkaloids
Labeling

Keywords

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

ASJC Scopus subject areas

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

Cite this

Aurintricarboxylic acid inhibits protein synthesis independent, sanguinarine-induced apoptosis and oncosis. / Hallock, Sarathi; Tang, Shou-Ching; Buja, L. Maximilian; Trump, Benjamin F.; Liepins, Andrejs; Weerasinghe, Priya.

In: Toxicologic Pathology, Vol. 35, No. 2, 12.03.2007, p. 300-309.

Research output: Contribution to journalArticle

Hallock, S, Tang, S-C, Buja, LM, Trump, BF, Liepins, A & Weerasinghe, P 2007, 'Aurintricarboxylic acid inhibits protein synthesis independent, sanguinarine-induced apoptosis and oncosis', Toxicologic Pathology, vol. 35, no. 2, pp. 300-309. https://doi.org/10.1080/01926230701194211
Hallock, Sarathi ; Tang, Shou-Ching ; Buja, L. Maximilian ; Trump, Benjamin F. ; Liepins, Andrejs ; Weerasinghe, Priya. / Aurintricarboxylic acid inhibits protein synthesis independent, sanguinarine-induced apoptosis and oncosis. In: Toxicologic Pathology. 2007 ; Vol. 35, No. 2. pp. 300-309.
@article{592cb7c05bb64897a3ec4d55b0dbb120,
title = "Aurintricarboxylic acid inhibits protein synthesis independent, sanguinarine-induced apoptosis and oncosis",
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.",
keywords = "Apoptosis, Aurintricarboxylic acid, Bimodal cell death, Cycloheximide, Necrosis, Oncosis, Sanguinarine",
author = "Sarathi Hallock and Shou-Ching Tang and Buja, {L. Maximilian} and Trump, {Benjamin F.} and Andrejs Liepins and Priya Weerasinghe",
year = "2007",
month = "3",
day = "12",
doi = "10.1080/01926230701194211",
language = "English (US)",
volume = "35",
pages = "300--309",
journal = "Toxicologic Pathology",
issn = "0192-6233",
publisher = "SAGE Publications Inc.",
number = "2",

}

TY - JOUR

T1 - Aurintricarboxylic acid inhibits protein synthesis independent, sanguinarine-induced apoptosis and oncosis

AU - Hallock, Sarathi

AU - Tang, Shou-Ching

AU - Buja, L. Maximilian

AU - Trump, Benjamin F.

AU - Liepins, Andrejs

AU - Weerasinghe, Priya

PY - 2007/3/12

Y1 - 2007/3/12

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Aurintricarboxylic acid

KW - Bimodal cell death

KW - Cycloheximide

KW - Necrosis

KW - Oncosis

KW - Sanguinarine

UR - http://www.scopus.com/inward/record.url?scp=33847774600&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847774600&partnerID=8YFLogxK

U2 - 10.1080/01926230701194211

DO - 10.1080/01926230701194211

M3 - Article

VL - 35

SP - 300

EP - 309

JO - Toxicologic Pathology

JF - Toxicologic Pathology

SN - 0192-6233

IS - 2

ER -