| In vitro evaluation of a p53-expressing adenovirus as an anti-cancer drug. | |
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MedLine Citation:
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PMID: 8707413 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Deficiency in p53-mediated cell death is common in human cancer, contributing to both tumorigenesis and chemoresistance. In an attempt to restore p53, we evaluated in vitro infectivity and cytotoxicity of a wild type (w.t.) p53-expressing adenovirus (Ad-p53) toward a panel of human cancer cell lines (n = 19). At a multiplicity of infection of 30, both Ad-p53 and adenovirus expressing beta-galactosidase (Ad-LacZ) infected greater than 99% of cells derived from brain, lung, breast, ovarian, colon, and prostate cancer, but failed to infect leukemia or lymphoma cells. Ad-p53, but not Ad-LacZ, infection of cancer cells was followed by nuclear accumulation of the CDK inhibitor p21WAFI/CIPI, cell cycle arrest and loss of viability. Ad-p53 induced apoptotic death in cancer cells that express mutant p53, including multi-drug resistant cells, but fewer deaths were observed in some w.t. p53 expressing cells. Ad-p53-infected SKBr3 breast cancer cells were more sensitive to cytotoxicity of the DNA damaging drugs mitomycin C or Adriamycin, but not the M-phase specific drug vincristine. Our results suggest that Ad-p53 is capable of infecting and killing cancer cells of diverse tissue origins (including multi-drug resistant cancer cells), that p21WAFI/CIPI may be a useful marker of p53 infectivity and that there may be synergy between Ad-p53 and either mitomycin C or Adriamycin induced cell death in tumors with p53 mutations. |
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Authors:
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M V Blagosklonny; W S el-Deiry |
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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: International journal of cancer. Journal international du cancer Volume: 67 ISSN: 0020-7136 ISO Abbreviation: Int. J. Cancer Publication Date: 1996 Jul |
Date Detail:
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Created Date: 1996-09-10 Completed Date: 1996-09-10 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 386-92 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Oncology and Cell Cycle Regulation, University of Pennsylvania Comprehensive Cancer Center, Philadelphia, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics*,
metabolism* Adenovirus Infections, Human / genetics, metabolism, virology Antineoplastic Agents / pharmacology Breast Neoplasms / genetics, therapy, virology Colonic Neoplasms / genetics, therapy, virology Cyclin-Dependent Kinase Inhibitor p21 Cyclins / analysis Drug Resistance, Multiple Evaluation Studies as Topic Genes, p53 Glioblastoma / genetics, therapy, virology Humans Lung Neoplasms / genetics, therapy, virology Neoplasms / genetics, therapy*, virology* Time Factors Tumor Cells, Cultured Tumor Suppressor Protein p53 / biosynthesis, genetics, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Tumor Suppressor Protein p53 |
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