| Methylseleninic acid potentiates apoptosis induced by chemotherapeutic drugs in androgen-independent prostate cancer cells. | |
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MedLine Citation:
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PMID: 15788689 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To test whether and how selenium enhances the apoptosis potency of selected chemotherapeutic drugs in prostate cancer (PCA) cells. EXPERIMENTAL DESIGN: DU145 and PC3 human androgen-independent PCA cells were exposed to minimal apoptotic doses of selenium and/or the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN38), the topoisomerase II inhibitor etoposide or the microtubule inhibitor paclitaxel/taxol. Apoptosis was measured by ELISA for histone-associated DNA fragments, by flow cytometric analysis of sub-G(1) fraction, and by immunoblot analysis of cleaved poly(ADP-ribose)polymerase. Pharmacologic inhibitors were used to manipulate caspases and c-Jun-NH(2)-terminal kinases (JNK). RESULTS: The methylselenol precursor methylseleninic acid (MSeA) increased the apoptosis potency of SN38, etoposide, or paclitaxel by several folds higher than the expected sum of the apoptosis induced by MSeA and each drug alone. The combination treatment did not further enhance JNK1/2 phosphorylation that was induced by each drug in DU145 cells. The JNK inhibitor SP600125 substantially decreased the activation of caspases and apoptosis induced by MSeA combination with SN38 or etoposide and completely blocked these events induced by MSeA/paclitaxel. The caspase-8 inhibitor zIETDfmk completely abolished apoptosis and caspase-9 and caspase-3 cleavage, whereas the caspase-9 inhibitor zLEHDfmk significantly decreased caspase-3 cleavage and apoptosis but had no effect on caspase-8 cleavage. None of these caspase inhibitors abolished JNK1/2 phosphorylation. A JNK-independent suppression of survivin by SN38 and etoposide, but not by paclitaxel, was also observed. In contrast to MSeA, selenite did not show any enhancing effect on the apoptosis induced by these drugs. CONCLUSIONS: MSeA enhanced apoptosis induced by cancer therapeutic drugs in androgen-independent PCA cells. In DU145 cells, the enhancing effect was primarily through interactions between MSeA and JNK-dependent targets to amplify the caspase-8-initiated activation cascades. The results suggest a novel use of methyl selenium for improving the chemotherapy of PCA. |
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Authors:
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Hongbo Hu; Cheng Jiang; Clement Ip; Youcef M Rustum; Junxuan Lü |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; 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: Clinical cancer research : an official journal of the American Association for Cancer Research Volume: 11 ISSN: 1078-0432 ISO Abbreviation: Clin. Cancer Res. Publication Date: 2005 Mar |
Date Detail:
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Created Date: 2005-03-24 Completed Date: 2005-06-30 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9502500 Medline TA: Clin Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 2379-88 Citation Subset: IM |
Affiliation:
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Hormel Institute, University of Minnesota, 801 16th Avenue Northeast, Austin, MN 55912, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Androgens
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chemistry Antineoplastic Agents, Phytogenic / pharmacology Apoptosis / drug effects* Camptothecin / analogs & derivatives*, pharmacology Caspases / drug effects, metabolism Drug Therapy, Combination Enzyme Activation / drug effects Etoposide / pharmacology Humans JNK Mitogen-Activated Protein Kinases / metabolism Male Organoselenium Compounds / pharmacology Paclitaxel / pharmacology Phosphorylation Poly(ADP-ribose) Polymerases / metabolism Prostatic Neoplasms / drug therapy, metabolism*, pathology Tumor Cells, Cultured p38 Mitogen-Activated Protein Kinases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA 92231/CA/NCI NIH HHS; CA 95642/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Androgens; 0/Antineoplastic Agents, Phytogenic; 0/Organoselenium Compounds; 0/SN38-Glu; 28274-57-9/methylselenic acid; 33069-62-4/Paclitaxel; 33419-42-0/Etoposide; 7689-03-4/Camptothecin; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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