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Biochemical and Biophysical Research Communications

Publication date: 2012-05
Volume: 421 Pages: 268 - 273
ISSN: 0006-291X, 1090-2104 PMID: 22507983
DOI: 10.1016/j.bbrc.2012.03.150
Publisher: Academic Press


Kviecinski, MR
Pedrosa, RC ; Felipe, KB ; Farias, MS ; Glorieux, Christ ; Valenzuela, M ; Sid, B ; Benites, J ; Valderrama, JA ; Verrax, Julien ; Buc Calderon, P


Antineoplastic Agents, Ascorbic Acid, Cell Line, Tumor, Cell Movement, Cell Proliferation, Humans, Naphthoquinones, Oxidation-Reduction, Oxidative Stress, Urinary Bladder, 0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 1101 Medical Biochemistry and Metabolomics, Biochemistry & Molecular Biology


The effects of juglone on T24 cells were assessed in the presence and absence of ascorbate. The EC(50) value for juglone at 24h decreased from 28.5μM to 6.3μM in the presence of ascorbate. In juglone-treated cells, ascorbate increased ROS formation (4-fold) and depleted GSH (65%). N-acetylcysteine or catalase restricted the juglone/ascorbate-mediated effects, highlighting the role of oxidative stress in juglone cytotoxicity. Juglone alone or associated with ascorbate did not cause caspase-3 activation or PARP cleavage, suggesting necrosis-like cell death. DNA damage and the mild ER stress caused by juglone were both enhanced by ascorbate. In cells treated with juglone (1-5μM), a concentration-dependent decrease in cell proliferation was observed. Ascorbate did not impair cell proliferation but its association with juglone led to a clonogenic death state. The motility of ascorbate-treated cells was not affected. Juglone slightly restricted motility, but cells lost their ability to migrate most noticeably when treated with juglone plus ascorbate. We postulate that juglone kills cells by a necrosis-like mechanism inhibiting cell proliferation and the motility of T24 cells. These effects are enhanced in the presence of ascorbate.