Influence of p53 and bcl-2 on chemosensitivity in benign and malignant prostatic cell lines

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dc.contributor.authorSerafin A.M.
dc.contributor.authorBohm L.
dc.date.accessioned2011-05-15T16:18:20Z
dc.date.available2011-05-15T16:18:20Z
dc.date.issued2005
dc.description.abstractThe administration of cancer chemotherapeutic agents results in an increase in the apoptotic cells in the tumor: therefore, it has been assumed that anticancer drugs exhibit their cytotoxic effects via apoptotic signaling pathways. Characteristics that confer sensitivity to drug-induced apoptosis are, a functional p53 protein and expression of the apoptosis-promoting protein, bax. The role of p53 and bax/bcl-2 in drug-induced apoptosis was assessed in six prostate cell lines, 1532T, 1535T, 1542T, 1542N, BPH-1 and LNCaP using TD 50 concentrations of etoposide, vinblastine and estramustine. Cell death was monitored morphologically by fluorescent microscopy, and by flow cytometry (Annexin-V assay). Apoptotic morphology was rather low and ranged from 0.1% to 12.1%, 3.0% to 6.0% and 0.1% to 8.5% for etoposide, estramustine and vinblastine, respectively. Annexin-V binding and flow cytometry indicated apoptotic propensities of 0% to 4%, 0% to 3% and 0% to 5%, respectively. The percentage of cells responding to drug-induced apoptosis was, on average, higher in the tumor cell lines than in the normal cell lines, but showed no correlation with p53 status. The percentage of cells showing necrosis, assessed by Annexin binding and Propidium Iodide permeability in aqueous medium, tended to be much higher, and was found to be at the level of 5% to 30%. Immunoblotting demonstrated that bax and bcl-2 proteins were expressed at a basal level in all cell lines, but did not increase after exposure to TD50 doses of the three drugs. The ratio of bax and bcl-2, measured by laser scanning densitometry, was not altered by the drug-induced DNA damage. The results suggest that apoptosis is not a major mechanism of drug-induced cell death in prostate cell lines and appears to be independent of p53 status and bax/bcl-2 expression. © 2005 Elsevier Inc. All rights reserved.
dc.description.versionArticle
dc.identifier.citationUrologic Oncology: Seminars and Original Investigations
dc.identifier.citation23
dc.identifier.citation2
dc.identifier.issn10781439
dc.identifier.other10.1016/j.urolonc.2004.11.007
dc.identifier.urihttp://hdl.handle.net/10019.1/14609
dc.subjectestramustine
dc.subjectestramustine phosphate
dc.subjectetoposide
dc.subjectprotein Bax
dc.subjectprotein bcl 2
dc.subjectprotein p53
dc.subjectvinblastine
dc.subjectantineoplastic activity
dc.subjectapoptosis
dc.subjectarticle
dc.subjectcell death
dc.subjectcell line
dc.subjectcell structure
dc.subjectchemosensitivity
dc.subjectconcentration response
dc.subjectcontrolled study
dc.subjectcorrelation analysis
dc.subjectDNA damage
dc.subjectdrug effect
dc.subjecthuman
dc.subjecthuman cell
dc.subjectmale
dc.subjectpriority journal
dc.subjectprostate cancer
dc.subjectprostate hypertrophy
dc.subjectprotein expression
dc.subjectprotein function
dc.subjectAntineoplastic Agents, Hormonal
dc.subjectAntineoplastic Agents, Phytogenic
dc.subjectApoptosis
dc.subjectDNA Damage
dc.subjectDose-Response Relationship, Drug
dc.subjectEstramustine
dc.subjectGene Expression Profiling
dc.subjectGenes, bcl-2
dc.subjectGenes, p53
dc.subjectHumans
dc.subjectMale
dc.subjectNecrosis
dc.subjectProstatic Hyperplasia
dc.subjectProstatic Neoplasms
dc.subjectTumor Cells, Cultured
dc.subjectVinblastine
dc.titleInfluence of p53 and bcl-2 on chemosensitivity in benign and malignant prostatic cell lines
dc.typeArticle
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