| Differential protection and transactivation of P53, P21, Bcl2, PCNA, cyclin G, and MDM2 genes in rat liver and the HepG2 cell line upon exposure to pifithrin. | |
| | |
MedLine Citation:
|
PMID: 17487067 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
In response to genotoxic agents, normal tissue cells are instructed by p53 either to perform DNA repair or to undergo apoptosis. Studies showed that chemo and/or radiotherapy damage both normal and cancerous cells indiscriminately. To this end, severe side effects inflicted by p53 activation in normal tissues, would possibly be abrogated by p53 inhibition. Pifithrin-alpha (PFT-alpha) is a reversible inhibitor of p53-mediated apoptosis, p53-dependent gene transcription, as well as down stream responsive gene function. The objective of this study was (1) to evaluate PFT-alpha for differential cellular protection in response to arsenic trioxide and cadmium chloride exposure of normal and neoplastic cells, and (2) to evaluate the transcriptional activation of p53 and p53-responsive genes in rat liver cells and HepG2 carcinoma cell line. Cell survival was detected by fluorescein diacetate (FDA) and fluorospectroscopy. Mean LC50 and (SD) for HepG2 cells following exposure to arsenic were 13.7 (+/-1.0) microg/ml with PFT- alpha and 13.4 (+/- 0.5) microg/ml without PFT-alpha (p>0.05). For rat liver cells it was 670 (+/- 8.15) microg/ml with and 573.15 (+/-1.0) microg/ml without PFT-alphha (p<0.05). On exposure to cadmium Chloride, LC50's were 6.95 (+/-2.5) microg/ml for HepG2 cell line in presence of PFT-alpha and 7.35 (+/-1.9) microg/ml in its absence (p>0.5). The results revealed significant differences from controls only upon exposure of rat liver cells to arsenic trioxide in presence of PFT-alpha. PFT-alpha inhibited the transactivation of p53 in rat liver cells and resulted in repression of Bcl2, PCNA, MDM2, Cyclin G and P21 genes by arsenic trioxide. HepG2 cells exposed to arsenic trioxide and PFT-alpha showed expression of only the P53 and PCNA genes. We conclude that PFT-alpha exhibits cytoprotective effect, modifies the detrimental influences of known genotoxic agents in normal cells and has the potential for use as an adjuvant to cancer therapy. |
| | |
Authors:
|
Ibrahim O Farah; Rowshan A Begum; Ali B Ishaque |
Related Documents
:
|
8453637 - P53 mutations selected in vivo when mouse mammary epithelial cells form hyperplastic ou... 10226577 - P53-independent anisomycin induced g1 arrest and apoptosis in l1210 cell lines. 15641097 - The magnitude of methylmercury-induced cytotoxicity and cell cycle arrest is p53-depend... 1809377 - Involvement of wild-type p53 protein in the cell cycle requires nuclear localization. 12701807 - L-canavanine as a radiosensitization agent for human pancreatic cancer cells. 10926287 - Functional mitochondrial heterogeneity in heteroplasmic cells carrying the mitochondria... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Biomedical sciences instrumentation Volume: 43 ISSN: 0067-8856 ISO Abbreviation: Biomed Sci Instrum Publication Date: 2007 |
Date Detail:
|
Created Date: 2007-05-09 Completed Date: 2007-06-13 Revised Date: 2009-11-11 |
Medline Journal Info:
|
Nlm Unique ID: 0140524 Medline TA: Biomed Sci Instrum Country: United States |
Other Details:
|
Languages: eng Pagination: 116-21 Citation Subset: IM |
Affiliation:
|
Department of Biology, Jackson State University, Jackson, MS 39217, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Arsenic / toxicity* Benzothiazoles / administration & dosage* Cadmium / toxicity* Cell Line, Tumor Cells, Cultured Cytoprotection / drug effects DNA Damage DNA Repair / drug effects* Dose-Response Relationship, Drug Drug Combinations Gene Expression Regulation / drug effects Hepatoblastoma / metabolism*, pathology Hepatocytes / drug effects, metabolism*, pathology Humans Lethal Dose 50 Liver Neoplasms Male Neoplasm Proteins / metabolism* Rats Rats, Wistar Toluene / administration & dosage, analogs & derivatives* Tumor Suppressor Protein p53 / antagonists & inhibitors |
| Chemical | |
Reg. No./Substance:
|
0/Benzothiazoles; 0/Drug Combinations; 0/Neoplasm Proteins; 0/Tumor Suppressor Protein p53; 0/pifithrin; 108-88-3/Toluene; 7440-38-2/Arsenic; 7440-43-9/Cadmium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Differential modulation of intracellular energetics in A549 and MRC-5 cells.
Next Document: An electronic location safety support system.