| Teriflunomide encourages cytostatic and apoptotic effects in premalignant and malignant cutaneous keratinocytes. | |
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MedLine Citation:
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PMID: 20544286 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Teriflunomide (TFN) reportedly inhibits de novo pyrimidine synthesis and exhibits anti-inflammatory, disease-modifying activities in vivo. These qualities would suggest that TFN could be useful in skin cancer chemoprevention or therapy. We investigated some mechanistic aspects of this tenet by characterizing the effects of TFN on premalignant and malignant human cutaneous keratinocytes. TFN promoted a dose- and/or time-dependent cytostasis and in these cells, which was followed by apoptosis. These features occurred in the presence of a physiological concentration of uridine in the culture medium. The short-term S phase arrest triggered by TFN was reversible in the malignant keratinocytes, and the indirect apoptosis induction was apparently preceded by mitochondrial disruption and reactive oxygen species production in both the premalignant and malignant keratinocytes. Respiration deficient malignant keratinocytes were resistant to the acute cytostatic and latent apoptotic effects of TFN implicating de novo pyrimidine synthesis and mitochondrial bioenergetics as the primary targets for TFN in the respiring cells. These novel mechanistic findings support a role for TFN in skin cancer chemoprevention and therapy. |
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Authors:
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Numsen Hail; Ping Chen; Joseph Rower; Lane R Bushman |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Apoptosis : an international journal on programmed cell death Volume: 15 ISSN: 1573-675X ISO Abbreviation: Apoptosis Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-01 Completed Date: 2010-12-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9712129 Medline TA: Apoptosis Country: United States |
Other Details:
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Languages: eng Pagination: 1234-46 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences, University of Colorado Denver School of Pharmacy, Aurora, CO 80045, USA. Numsen.Hail@UCDenver.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology*,
therapeutic use Antioxidants / pharmacology Apoptosis* Carcinoma, Squamous Cell / drug therapy, metabolism, pathology, prevention & control Cell Cycle / drug effects Cell Line, Tumor Crotonic Acids / pharmacology*, therapeutic use Cytostatic Agents / pharmacology Energy Metabolism / drug effects Epithelial Cells / drug effects Flow Cytometry Humans Keratinocytes / cytology, drug effects*, metabolism, pathology Mitochondria / drug effects, metabolism Oxygen Consumption / drug effects Precancerous Conditions / drug therapy, metabolism, pathology* Pyrimidines / biosynthesis Reactive Oxygen Species / metabolism S Phase Skin Neoplasms / drug therapy, metabolism, pathology*, prevention & control Toluidines / pharmacology*, therapeutic use Uridine / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Antioxidants; 0/Crotonic Acids; 0/Cytostatic Agents; 0/Pyrimidines; 0/Reactive Oxygen Species; 0/Toluidines; 0/teriflunomide; 289-95-2/pyrimidine; 58-96-8/Uridine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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