Aurintricarboxylic acid inhibits protein synthesis independent, sanguinarine-induced apoptosis and oncosis.
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.
Hallock
Sarathi
S
Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, A1B 3V6, Canada.
Tang
Shou-Ching
SC
Buja
L Maximilian
LM
Trump
Benjamin F
BF
Liepins
Andrejs
A
Weerasinghe
Priya
P
D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D053119:Benzophenanthridines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D003850:Deoxyribonuclease I / Q000037:antagonists & inhibitors / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology / Q000503:physiopathology; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*
D000470:Alkaloids; D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D007546:Isoquinolines; D011500:Protein Synthesis Inhibitors; D001312:Aurintricarboxylic Acid; D003513:Cycloheximide; C005705:sanguinarine; D003850:Deoxyribonuclease I