| Gefitinib induces apoptosis and decreases telomerase activity in MDA-MB-231 human breast cancer cells. | |
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MedLine Citation:
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PMID: 19898796 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Gefitinib is an anti-cancer drug that selectively inhibits epithelial growth factor receptor (EGFR) tyrosine kinase activity and induces apoptosis in many cancer cells. Cancer cells are often protected from apoptotic cell death by telomerase, however the gefitinib-induced telomerase inhibition remains unknown. Here we investigated the effects of gefitinib on telomerase activity in two different breast cancer lines, MCF-7 (low expression of EGFR) and MDA-MB-231 (high expression of EGFR). We observed the inhibition of EGFR phosphorylation that occurred only MDA-MB-231 cells cultured in media containing 10% FBS. Direct cytotoxicity was observed in MDA-MB-231 cells, but not MCF-7 cells when treated with concentrations of gefitinib ranging from 15 to 20 microM. This cytotoxicity was associated with decreased telomerase activity and downregulation of the telomerase subunit, hTERT. c-Myc has previously been shown to activate telomerase activity through transcriptional regulation of hTERT. A decrease in c-myc expression and DNA-binding activity following treatment with gefitinib was observed exclusively in MDA-MB-231 cells. We also demonstrated that gefitinib downregulates the activation of Akt and subsequent hTERT phosphorylation and translocation into the nucleus in MDA-MB-231 cells. These results indicate that gefitinib induces loss of telomerase activity through dephosphorylation of EGFR in MDA-MB-231 cells. |
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Authors:
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Dong-Oh Moon; Mun-Ock Kim; Moon-Soo Heo; Jae-Dong Lee; Yung Hyun Choi; Gi-Young Kim |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-08 |
Journal Detail:
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Title: Archives of pharmacal research Volume: 32 ISSN: 0253-6269 ISO Abbreviation: Arch. Pharm. Res. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-11-09 Completed Date: 2010-01-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8000036 Medline TA: Arch Pharm Res Country: Korea (South) |
Other Details:
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Languages: eng Pagination: 1351-60 Citation Subset: IM |
Affiliation:
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Department of Marine Life Sciences, Jeju National University, Jeju, Korea. |
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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pharmacology* Apoptosis / drug effects* Blotting, Western Breast Neoplasms / enzymology*, pathology* Cell Line, Tumor Cell Survival / drug effects Female Humans Phosphorylation Quinazolines / pharmacology* Receptor, Epidermal Growth Factor / antagonists & inhibitors Reverse Transcriptase Polymerase Chain Reaction Telomerase / antagonists & inhibitors* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Quinazolines; 184475-35-2/gefitinib; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase |
| Comments/Corrections | |
Comment In:
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Arch Pharm Res. 2009 Oct;32(10):1333-4
[PMID:
19898793
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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