| Arsenic trioxide suppresses thymidylate synthase in 5-FU-resistant colorectal cancer cell line HT29 In Vitro re-sensitizing cells to 5-FU. | |
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MedLine Citation:
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PMID: 20530422 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Identification of new agents with antitumor activity in chemoresistant tumors is urgently needed for the treatment of colorectal cancer. Arsenic trioxide (As(2)O(3)), a Food and Drug Administration (FDA) approved drug is successfully being used to treat acute promyelocytic leukemia (APL). Several clinical trials also suggest its ineffectiveness on solid tumors. We proposed that arsenic trioxide may be used as chemosensitizer, especially to 5-fluorouracil (5-FU). The effect of arsenic trioxide on cell proliferation of 5-FU-sensitive and -resistant HT29 colorectal cancer cells in vitro was tested by trypan blue dye exclusion assay, 2, 3-bis(2-methoxy-4-nitro-5-sulfophenyl)-S-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide (XTT) cell proliferation assay and cell cycle analysis using flow cytometry. Gene expression was analyzed using real-time polymerase chain reaction (PCR) and Western blot methods. There was a dose-dependent increase in cell detachment and proliferation in HT29 and HT29FU cells. As a single agent, arsenic trioxide also down-regulated thymidylate synthase (TS) expression without affecting the expression of some other genes analyzed in the above cell lines. Combination of arsenic trioxide and 5-FU increased cytotoxicity. In vitro data show that as a single agent, arsenic trioxide down-regulated TS expression in HT29 cells. Addition of 5-FU to these sensitized cells increased cytotoxicity. These findings open up a possibility to use arsenic trioxide as a chemosensitizer in combination therapy. |
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Authors:
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Pochi Ramalingam Subbarayan; Kelvin Lee; Bach Ardalan |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Anticancer research Volume: 30 ISSN: 1791-7530 ISO Abbreviation: Anticancer Res. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-06-09 Completed Date: 2010-06-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: Greece |
Other Details:
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Languages: eng Pagination: 1157-62 Citation Subset: IM |
Affiliation:
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Department of Medicine, Division of Hematology and Oncology, University of Miami School of Medicine, Miami, FL 33136, USA. spochi@med.miami.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Combined Chemotherapy Protocols
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pharmacology* Arsenicals / administration & dosage, pharmacology* Blotting, Western Colorectal Neoplasms / drug therapy*, enzymology* Drug Resistance, Neoplasm Drug Synergism Fluorouracil / administration & dosage, pharmacology* Gene Expression / drug effects HT29 Cells Humans Oxides / administration & dosage, pharmacology* RNA, Messenger / biosynthesis, genetics Reverse Transcriptase Polymerase Chain Reaction Thymidylate Synthase / antagonists & inhibitors*, biosynthesis, genetics Tumor Suppressor Protein p53 / biosynthesis, genetics |
| Chemical | |
Reg. No./Substance:
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0/Arsenicals; 0/Oxides; 0/RNA, Messenger; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 1327-53-3/arsenic trioxide; 51-21-8/Fluorouracil; EC 2.1.1.45/Thymidylate Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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