Abstract | PURPOSE: Current standard chemotherapeutic regimens for malignant melanoma are unsatisfactory. Although in vitro studies of arsenic trioxide (ATO) have demonstrated promise against melanoma, recent phase II clinical trials have failed to show any significant clinical benefit when used as a single agent. To enhance the efficacy of ATO in the treatment of melanoma, we sought to identify compounds that potentiate the cytotoxic effects of ATO in melanoma cells. Through a screen of 2,000 marketed drugs and naturally occurring compounds, a variety of antibiotic inhibitors of mitochondrial protein translation were identified. METHODS: RESULTS: CONCLUSIONS: Our data suggest that thiostrepton enhances the cytotoxic effects of ATO through a ROS-dependent mechanism. Co-administration of oxidative stress-inducing drugs such as thiostrepton in order to enhance the efficacy of ATO in the treatment of melanoma warrants further investigation.
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Authors | Benjamin D Bowling, Nicole Doudican, Prashiela Manga, Seth J Orlow |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 63
Issue 1
Pg. 37-43
(Dec 2008)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 18297286
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Arsenicals
- Mitochondrial Proteins
- Oxides
- Protein Synthesis Inhibitors
- Reactive Oxygen Species
- Tetracyclines
- Poly Adenosine Diphosphate Ribose
- Electron Transport Complex IV
- Thiostrepton
- Arsenic Trioxide
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Topics |
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Arsenic Trioxide
- Arsenicals
(pharmacology)
- Cell Line, Tumor
(drug effects)
- Drug Evaluation, Preclinical
- Drug Resistance, Neoplasm
(drug effects)
- Drug Synergism
- Electron Transport Complex IV
(metabolism)
- Humans
- Inhibitory Concentration 50
- Melanoma
(pathology)
- Mitochondrial Proteins
(antagonists & inhibitors, biosynthesis, genetics)
- Oxides
(pharmacology)
- Poly Adenosine Diphosphate Ribose
(metabolism)
- Protein Biosynthesis
(drug effects)
- Protein Synthesis Inhibitors
(pharmacology)
- Reactive Oxygen Species
(metabolism)
- Tetracyclines
(pharmacology)
- Thiostrepton
(pharmacology)
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