| Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. | |
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MedLine Citation:
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PMID: 11697818 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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HPMPC (cidofovir, CDV) is an acyclic nucleoside phosphonate (ANP) with broad-spectrum activity against DNA viruses, including human papillomavirus (HPV). HPMPC has proved to be effective in the treatment of HPV-associated disease in several clinical investigations. In vitro, treatment of HPV-positive cells (compared with normal primary human keratinocytes) with HPMPC has resulted in a concentration- and time-dependent inhibition of cell proliferation. We have now evaluated the mechanism by which this compound induces cell death. Different parameters of apoptosis, that is, (i) induction of CPP32 (caspase-3) protease activity, (ii) translocation of phosphatidylserine (PS) from the inner part of the plasma membrane to the outer layer, (iii) disintegration of the nuclear matrix protein (NMP), (iv) DNA fragmentation, (v) number of cells in apoptotic phase following cell cycle analysis, showed that the mechanism of cell death following treatment with CDV is based on apoptosis. Annexin V staining showed that induction of apoptosis in HPV-positive cells was correlated with a decrease in the percentage of viable cells, while no significant changes in the percentages of living cells were noted in primary human keratinocytes (PHK) cell cultures. Furthermore, a remarkable accumulation of HPMPC-treated cells in the S phase of the cell cycle was observed. Apoptosis induction and S phase arrest were concentration and time dependent. Induction of apoptosis in HPV-positive cells by HPMPC was associated with accumulation of the tumor suppressor protein p53 and the cyclin-dependent kinase inhibitor p21/WAF-1. As HPMPC has proved to induce apoptosis, in a time- and concentration-dependent manner, in a number of HPV-positive cell lines, the regression of papillomatous lesions observed with HPMPC in patients may be due, at least in part, to the induction of apoptosis. |
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Authors:
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G Andrei; R Snoeck; D Schols; E De Clercq |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncology research Volume: 12 ISSN: 0965-0407 ISO Abbreviation: Oncol. Res. Publication Date: 2000 |
Date Detail:
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Created Date: 2001-11-07 Completed Date: 2002-04-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9208097 Medline TA: Oncol Res Country: United States |
Other Details:
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Languages: eng Pagination: 397-408 Citation Subset: IM |
Affiliation:
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Rega Institute for Medical Reseach, K.U. Leuven, Belgium. graciela.andrei@rega.kuleuven.ac.be |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Annexin A5
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pharmacology Antiviral Agents / pharmacology* Apoptosis* Caspase 3 Caspases / biosynthesis Cell Cycle Cell Line Cell Nucleus / metabolism Cells, Cultured Cytosine / analogs & derivatives*, pharmacology* DNA Fragmentation Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Flow Cytometry Humans Keratinocytes / cytology*, virology* Organophosphorus Compounds / pharmacology* Papillomaviridae / metabolism* Phosphatidylserines / metabolism Phosphonic Acids* Proto-Oncogene Proteins p21(ras) / metabolism S Phase Time Factors Transfection Tumor Suppressor Protein p53 / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Annexin A5; 0/Antiviral Agents; 0/Organophosphorus Compounds; 0/Phosphatidylserines; 0/Phosphonic Acids; 0/Tumor Suppressor Protein p53; 113852-37-2/cidofovir; 71-30-7/Cytosine; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.6.5.2/HRAS protein, human; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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