| Inhibition of GSK-3β reverses the pro-apoptotic effect of proadifen (SKF-525A) in HT-29 colon adenocarcinoma cells. | |
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MedLine Citation:
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PMID: 22683934 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Proadifen (SKF-525A) is a well-known inhibitor of cytochrome P450 monooxygenases. Besides the prevention of drug metabolism it affects the proliferation of cancer cells, although the mechanisms of possible anti-cancer activity of proadifen have not however been fully understood yet. The aim of this study therefore was to evaluate the potential anti-proliferative effect of proadifen on HT-29 colon cancer cells. Our results show that proadifen inhibited the growth of HT-29 cells by the accumulation of cells in the G1 phase of the cell cycle, reduction of metabolic activity and colony formation and by the induction of apoptosis. Analyses of Western blots and flow cytometry revealed time- and dose-dependent phosphatidylserine externalization, caspase-3 activation and PARP cleavage. Intense upregulation of NAG-1 and ATF3 and downregulation of Mcl-1 and Egr-1 were also observed. Further investigation showed that NAG-1 gene silencing by siRNA had no effect on the pro-apoptotic action of proadifen. In contrast, we found that AR-A014418, the specific inhibitor of glycogen synthase kinase-3 β (GSK-3β), significantly decreased proadifen-induced apoptosis. Inactivation of GSK-3β (phosphorylation at serine 9) resulted in changes in phosphatidylserine externalization and caspase-3 activation. These data suggest that GSK-3β is an important factor in the induction of apoptosis in HT-29 colon cancer cells treated with proadifen. |
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Authors:
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Rastislav Jendželovský; Ján Kovaľ; Jaromír Mikeš; Zuzana Papčová; Jana Plšíková; Peter Fedoročko |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-6-6 |
Journal Detail:
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Title: Toxicology in vitro : an international journal published in association with BIBRA Volume: - ISSN: 1879-3177 ISO Abbreviation: - Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-6-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8712158 Medline TA: Toxicol In Vitro Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier Ltd. |
Affiliation:
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Institute of Biology and Ecology, Department of Cellular Biology, Pavol Jozef Šafárik University in Košice, Slovakia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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