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Aurintricarboxylic Acid Inhibits Protein Synthesis Independent, Sanguinarine-Induced Apoptosis and Oncosis

¹ Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, A1B 3V6, Canada
² Baylor College of Medicine, Department of Medicine, Houston, TX 77030, USA
³ University of Texas Health Sciences Center at Houston, Houston, TX 77030, USA
⁴ AMC Cancer Research Center, Denver, CO 80214, USA

Correspondence: Address correspondence to: Priya Weerasinghe, Baylor College of Medicine, Department of Medicine, BCM 286, N 1319, 1 Baylor Plaza, Houston, Texas 77030, USA; e-mail:priyaw{at}bcm.tmc.edu

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.

Key Words: Oncosis • apoptosis • necrosis • bimodal cell death • sanguinarine • aurintricarboxylic acid • cycloheximide

Abbreviations: ATA, Aurin Tricarboxylic Acid • CHX, Cycloheximide • BCD, Blister Cell Death • DCS, Diffuse Cell Swelling • BMCD, Bimodal Cell Death

Toxicologic Pathology, Vol. 35, No. 2, 300-309 (2007)
DOI: 10.1080/01926230701194211


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