| EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. | |
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MedLine Citation:
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PMID: 15711178 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In this study, we show that the novel synthetic curcumin analog, EF24, induces cell cycle arrest and apoptosis by means of a redox-dependent mechanism in MDA-MB-231 human breast cancer cells and DU-145 human prostate cancer cells. Cell cycle analysis demonstrated that EF24 causes a G2/M arrest in both cell lines, and that this cell cycle arrest is followed by the induction of apoptosis as evidenced by caspase-3 activation, phosphatidylserine externalization and an increased number of cells with a sub-G1 DNA fraction. In addition, we demonstrate that EF24 induces a depolarization of the mitochondrial membrane potential, suggesting that the compound may also induce apoptosis by altering mitochondrial function. EF24, like curcumin, serves as a Michael acceptor reacting with glutathione (GSH) and thioredoxin 1. Reaction of EF24 with these agents in vivo significantly reduced intracellular GSH as well as oxidized GSH in both the wild-type and Bcl-xL overexpressing HT29 human colon cancer cells. We therefore propose that the anticancer effect of a novel curcumin analog, EF24, is mediated in part by redox-mediated induction of apoptosis. |
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Authors:
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Brian K Adams; Jiyang Cai; Jeff Armstrong; Marike Herold; Yang J Lu; Aiming Sun; James P Snyder; Dennis C Liotta; Dean P Jones; Mamoru Shoji |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Anti-cancer drugs Volume: 16 ISSN: 0959-4973 ISO Abbreviation: Anticancer Drugs Publication Date: 2005 Mar |
Date Detail:
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Created Date: 2005-02-15 Completed Date: 2005-05-24 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9100823 Medline TA: Anticancer Drugs Country: England |
Other Details:
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Languages: eng Pagination: 263-75 Citation Subset: IM |
Affiliation:
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Program in Molecular and Systems Pharmacology, Emory University, Atlanta, GA 30322, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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therapeutic use* Apoptosis / drug effects* Breast Neoplasms / drug therapy*, metabolism Caspase 3 Caspases / metabolism Cell Cycle / drug effects Colonic Neoplasms / drug therapy*, metabolism Curcumin / analogs & derivatives* Female Humans Male Oxidation-Reduction Prostatic Neoplasms / drug therapy*, metabolism Reactive Oxygen Species / metabolism Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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CA82995/CA/NCI NIH HHS; ES 09047/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Reactive Oxygen Species; 458-37-7/Curcumin; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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