Effects of Flutamide on [Methyl-3H]-Choline Uptake in Human Prostate Cancer-3 Cells: A Pilot Study
Identifieur interne : 002276 ( Pmc/Corpus ); précédent : 002275; suivant : 002277Effects of Flutamide on [Methyl-3H]-Choline Uptake in Human Prostate Cancer-3 Cells: A Pilot Study
Auteurs : Fatma Al-SaeediSource :
- Current Therapeutic Research, Clinical and Experimental [ 0011-393X ] ; 2007.
Abstract
Url:
DOI: 10.1016/j.curtheres.2007.08.003
PubMed: 24683213
PubMed Central: 3967349
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effects of Flutamide on [Methyl-<sup>3</sup>H]-Choline Uptake in Human Prostate Cancer-3 Cells: A Pilot Study</title><author><name sortKey="Al Saeedi, Fatma" sort="Al Saeedi, Fatma" uniqKey="Al Saeedi F" first="Fatma" last="Al-Saeedi">Fatma Al-Saeedi</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24683213</idno><idno type="pmc">3967349</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967349</idno><idno type="RBID">PMC:3967349</idno><idno type="doi">10.1016/j.curtheres.2007.08.003</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">002276</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002276</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Effects of Flutamide on [Methyl-<sup>3</sup>H]-Choline Uptake in Human Prostate Cancer-3 Cells: A Pilot Study</title><author><name sortKey="Al Saeedi, Fatma" sort="Al Saeedi, Fatma" uniqKey="Al Saeedi F" first="Fatma" last="Al-Saeedi">Fatma Al-Saeedi</name></author></analytic><series><title level="j">Current Therapeutic Research, Clinical and Experimental</title><idno type="ISSN">0011-393X</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> Positron emission tomography using [methyl-<sup>11</sup>C]-choline is effective in imaging many types of cancer, especially prostate cancer (PC). The antiandrogen flutamide is often used as part of the initial treatment of PC. Data on the effect of flutamide on and methylcholine incorporation into PC-3 cells are lacking in the experimental and literature work.</p><p><bold>Objectives:</bold> The aims of this study were to assess whether human PC-3 cells are susceptible to flutamide and whether the drug modulates the uptake of [methyl-<sup>3</sup>H]-choline into these cells.</p><p><bold>Methods:</bold> PC-3 cells were treated for 3 days with flutamide (≤100 nmol/L), inhibiting growth by 20% to 70% with control cells included. Two viability tests (cytotoxic analyses), the thiazole blue assay and the trypan blue exclusion method, were used to determine the median inhibitory concentration for flutamide (10 nmol/L). Control and flutamide-treated cells were incubated with [methyl-<sup>3</sup>H]-choline for 10 minutes and then in nonradioactive medium for 10 minutes to simulate the rapid blood clearance of [methyl-<sup>11</sup>C]-choline tracer that occurs within 5 to 20 minutes, and then extracted using organic and aqueous solvents to determine the intracellular distribution of the tracer. Protein assay and flow-cytometry analysis were used to determine protein content and DNA synthesis in both control and treated cells. The uptake of [methyl-<sup>3</sup>H]-choline was normalized to protein content and expressed as mean (SD) dpm/1Jg protein (n = 6).</p><p><bold>Results:</bold> PC-3 cell proliferation was inhibited with flutamide treatment. After treatment of PC-3 cells with flutamide 10 nmol/L for 3 days, cells accumulated DNA during the S phase. Mean (SD) [methyl-<sup>3</sup>H]-choline uptake was found to be significantly lower with flutamide 10-nmol/L-treated cells compared with control cells (65.95 [0.72] vs 114.21 [0.57] dpm/1Jg protein; <italic>P</italic> < 0.001); the difference between the 5-nmol/L-treated cells and controls was nonsignificant.</p><p><bold>Conclusions:</bold> In this pilot study, flutamide inhibited tumor cell growth and proliferation and decreased (modulated) the uptake of [methyl-<sup>3</sup>H]-choline into androgen receptor-negative PC-3 cells. These results suggest that flutamide might inhibit proliferation by an androgen-independent mechanism.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Curr Ther Res Clin Exp</journal-id><journal-id journal-id-type="iso-abbrev">Curr Ther Res Clin Exp</journal-id><journal-title-group><journal-title>Current Therapeutic Research, Clinical and Experimental</journal-title></journal-title-group><issn pub-type="ppub">0011-393X</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24683213</article-id><article-id pub-id-type="pmc">3967349</article-id><article-id pub-id-type="publisher-id">S0011-393X(07)00066-5</article-id><article-id pub-id-type="doi">10.1016/j.curtheres.2007.08.003</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Effects of Flutamide on [Methyl-<sup>3</sup>H]-Choline Uptake in Human Prostate Cancer-3 Cells: A Pilot Study</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Al-Saeedi</surname><given-names>Fatma</given-names></name><degrees>PhD</degrees><email>Fatimas@hsc.edu.kw</email><xref rid="cor1" ref-type="corresp">*</xref></contrib></contrib-group><aff>Nuclear Medicine Department, Faculty of Medicine, Kuwait University Health Sciences Center, Safat, Kuwait</aff><author-notes><corresp id="cor1"><label>*</label><bold>Address correspondence to:</bold> Fatma Al-Saeedi, PhD, Nuclear Medicine Department, Faculty of Medicine, Kuwait University Health Sciences Center, PO Box 24923, 13110 Safat, Kuwait. <email>Fatimas@hsc.edu.kw</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>1</day><month>7</month><year>2007</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>7</month><year>2007</year></pub-date><volume>68</volume><issue>4</issue><fpage>226</fpage><lpage>241</lpage><history><date date-type="accepted"><day>7</day><month>8</month><year>2007</year></date></history><permissions><copyright-statement>© 2007 The Authors. Published by Elsevier Inc. All rights reserved.</copyright-statement><copyright-year>2007</copyright-year><copyright-holder>Excerpta Medica, Inc.</copyright-holder></permissions><abstract><p><bold>Background:</bold> Positron emission tomography using [methyl-<sup>11</sup>C]-choline is effective in imaging many types of cancer, especially prostate cancer (PC). The antiandrogen flutamide is often used as part of the initial treatment of PC. Data on the effect of flutamide on and methylcholine incorporation into PC-3 cells are lacking in the experimental and literature work.</p><p><bold>Objectives:</bold> The aims of this study were to assess whether human PC-3 cells are susceptible to flutamide and whether the drug modulates the uptake of [methyl-<sup>3</sup>H]-choline into these cells.</p><p><bold>Methods:</bold> PC-3 cells were treated for 3 days with flutamide (≤100 nmol/L), inhibiting growth by 20% to 70% with control cells included. Two viability tests (cytotoxic analyses), the thiazole blue assay and the trypan blue exclusion method, were used to determine the median inhibitory concentration for flutamide (10 nmol/L). Control and flutamide-treated cells were incubated with [methyl-<sup>3</sup>H]-choline for 10 minutes and then in nonradioactive medium for 10 minutes to simulate the rapid blood clearance of [methyl-<sup>11</sup>C]-choline tracer that occurs within 5 to 20 minutes, and then extracted using organic and aqueous solvents to determine the intracellular distribution of the tracer. Protein assay and flow-cytometry analysis were used to determine protein content and DNA synthesis in both control and treated cells. The uptake of [methyl-<sup>3</sup>H]-choline was normalized to protein content and expressed as mean (SD) dpm/1Jg protein (n = 6).</p><p><bold>Results:</bold> PC-3 cell proliferation was inhibited with flutamide treatment. After treatment of PC-3 cells with flutamide 10 nmol/L for 3 days, cells accumulated DNA during the S phase. Mean (SD) [methyl-<sup>3</sup>H]-choline uptake was found to be significantly lower with flutamide 10-nmol/L-treated cells compared with control cells (65.95 [0.72] vs 114.21 [0.57] dpm/1Jg protein; <italic>P</italic> < 0.001); the difference between the 5-nmol/L-treated cells and controls was nonsignificant.</p><p><bold>Conclusions:</bold> In this pilot study, flutamide inhibited tumor cell growth and proliferation and decreased (modulated) the uptake of [methyl-<sup>3</sup>H]-choline into androgen receptor-negative PC-3 cells. These results suggest that flutamide might inhibit proliferation by an androgen-independent mechanism.</p></abstract><kwd-group><title>Key words</title><kwd>flutamide</kwd><kwd>tumor</kwd><kwd>PET</kwd><kwd>radiopharmaceuticals</kwd><kwd>[methyl-<sup>3</sup>H]-choline</kwd><kwd>PC-3 cells</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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