Differential Cytotoxic Activity of a Novel Palladium-Based Compound on Prostate Cell Lines, Primary Prostate Epithelial Cells and Prostate Stem Cells
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{"title"=>"Differential Cytotoxic Activity of a Novel Palladium-Based Compound on Prostate Cell Lines, Primary Prostate Epithelial Cells and Prostate Stem Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Engin", "last_name"=>"Ulukaya", "scopus_author_id"=>"6602927353"}, {"first_name"=>"Fiona M.", "last_name"=>"Frame", "scopus_author_id"=>"8738387000"}, {"first_name"=>"Buse", "last_name"=>"Cevatemre", "scopus_author_id"=>"55693788600"}, {"first_name"=>"Davide", "last_name"=>"Pellacani", "scopus_author_id"=>"36473841000"}, {"first_name"=>"Hannah", "last_name"=>"Walker", "scopus_author_id"=>"24175172400"}, {"first_name"=>"Vincent M.", "last_name"=>"Mann", "scopus_author_id"=>"55642959000"}, {"first_name"=>"Matthew S.", "last_name"=>"Simms", "scopus_author_id"=>"7101913763"}, {"first_name"=>"Michael J.", "last_name"=>"Stower", "scopus_author_id"=>"7003957358"}, {"first_name"=>"Veysel T.", "last_name"=>"Yilmaz", "scopus_author_id"=>"7006269202"}, {"first_name"=>"Norman J.", "last_name"=>"Maitland", "scopus_author_id"=>"7006498464"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23675532", "doi"=>"10.1371/journal.pone.0064278", "sgr"=>"84877633486", "isbn"=>"10.1371/journal.pone.0064278", "scopus"=>"2-s2.0-84877633486", "issn"=>"19326203", "pui"=>"368893009"}, "id"=>"b82ab50d-03d5-3949-8ba4-792cb7b82dde", "abstract"=>"The outcome for patients with advanced metastatic and recurrent prostate cancer is still poor. Therefore, new chemotherapeutics are required, especially for killing cancer stem cells that are thought to be responsible for disease recurrence. In this study, we screened the effect of a novel palladium-based anticancer agent (Pd complex) against six different prostate cancer cell lines, and primary cultures from seven Gleason 6/7 prostate cancer, three Gleason 8/9 prostate cancer and four benign prostate hyperplasia patient samples, as well as cancer stem cells selected from primary cultures. MTT and ATP viability assays were used to assess cell growth and flow cytometry to assess cell cycle status. In addition, immunofluorescence was used to detect γH2AX nuclear foci, indicative of DNA damage, and Western blotting to assess the induction of apoptosis and autophagy. The Pd complex showed a powerful growth-inhibitory effect against both cell lines and primary cultures. More importantly, it successfully reduced the viability of cancer stem cells as first reported in this study. The Pd complex induced DNA damage and differentially induced evidence of cell death, as well as autophagy. In conclusion, this novel agent may be promising for use against the bulk of the tumour cell population as well as the prostate cancer stem cells, which are thought to be responsible for the resistance of metastatic prostate cancer to chemotherapy. This study also indicates that the combined use of the Pd complex with an autophagy modulator may be a more promising approach to treat prostate cancer. In addition, the differential effects observed between cell lines and primary cells emphasise the importance of the model used to test novel drugs including its genetic background, and indeed the necessity of using cells cultured from patient samples.", "link"=>"http://www.mendeley.com/research/differential-cytotoxic-activity-novel-palladiumbased-compound-prostate-cell-lines-primary-prostate-e", "reader_count"=>24, "reader_count_by_academic_status"=>{"Researcher"=>1, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>1, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Researcher"=>1, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>1, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Nursing and Health Professions"=>1, "Mathematics"=>1, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>9, "Chemistry"=>4}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Chemistry"=>{"Chemistry"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Mathematics"=>{"Mathematics"=>1}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Ireland"=>1, "South Africa"=>1, "Russia"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/1058650"], "description"=>"<p>IC<sub>50</sub> values of the Pd complex in cell lines.</p>", "links"=>[], "tags"=>["Molecular cell biology", "chemical biology", "medicinal chemistry", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "toxicology", "urology", "pd"], "article_id"=>701346, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Engin Ulukaya", "Fiona M. Frame", "Buse Cevatemre", "Davide Pellacani", "Hannah Walker", "Vincent M. Mann", "Matthew S. Simms", "Michael J. Stower", "Veysel T. Yilmaz", "Norman J. Maitland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0064278.t003", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IC_50_values_of_the_Pd_complex_in_cell_lines_/701346", "title"=>"IC<sub>50</sub> values of the Pd complex in cell lines.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-10 00:22:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1058651"], "description"=>"<p>C = Cystectomy/T = Transurethral resection of the prostate/R = Radical Prostatectomy/chT = channel TURP.</p>", "links"=>[], "tags"=>["Molecular cell biology", "chemical biology", "medicinal chemistry", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "toxicology", "urology", "epithelial"], "article_id"=>701347, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Engin Ulukaya", "Fiona M. Frame", "Buse Cevatemre", "Davide Pellacani", "Hannah Walker", "Vincent M. Mann", "Matthew S. Simms", "Michael J. Stower", "Veysel T. Yilmaz", "Norman J. Maitland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0064278.t002", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primary_epithelial_cells_/701347", "title"=>"Primary epithelial cells.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-10 00:22:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1058652"], "description"=>"<p>Cell lines.</p>", "links"=>[], "tags"=>["Molecular cell biology", "chemical biology", "medicinal chemistry", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "toxicology", "urology"], "article_id"=>701348, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Engin Ulukaya", "Fiona M. Frame", "Buse Cevatemre", "Davide Pellacani", "Hannah Walker", "Vincent M. Mann", "Matthew S. Simms", "Michael J. Stower", "Veysel T. Yilmaz", "Norman J. Maitland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0064278.t001", "stats"=>{"downloads"=>5, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cell_lines_/701348", "title"=>"Cell lines.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-10 00:22:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1058653", "https://ndownloader.figshare.com/files/1058654", "https://ndownloader.figshare.com/files/1058655"], "description"=>"<div><p>The outcome for patients with advanced metastatic and recurrent prostate cancer is still poor. Therefore, new chemotherapeutics are required, especially for killing cancer stem cells that are thought to be responsible for disease recurrence. In this study, we screened the effect of a novel palladium-based anticancer agent (Pd complex) against six different prostate cancer cell lines, and primary cultures from seven Gleason 6/7 prostate cancer, three Gleason 8/9 prostate cancer and four benign prostate hyperplasia patient samples, as well as cancer stem cells selected from primary cultures. MTT and ATP viability assays were used to assess cell growth and flow cytometry to assess cell cycle status. In addition, immunofluorescence was used to detect γH2AX nuclear foci, indicative of DNA damage, and Western blotting to assess the induction of apoptosis and autophagy. The Pd complex showed a powerful growth-inhibitory effect against both cell lines and primary cultures. More importantly, it successfully reduced the viability of cancer stem cells as first reported in this study. The Pd complex induced DNA damage and differentially induced evidence of cell death, as well as autophagy. In conclusion, this novel agent may be promising for use against the bulk of the tumour cell population as well as the prostate cancer stem cells, which are thought to be responsible for the resistance of metastatic prostate cancer to chemotherapy. This study also indicates that the combined use of the Pd complex with an autophagy modulator may be a more promising approach to treat prostate cancer. In addition, the differential effects observed between cell lines and primary cells emphasise the importance of the model used to test novel drugs including its genetic background, and indeed the necessity of using cells cultured from patient samples.</p></div>", "links"=>[], "tags"=>["Molecular cell biology", "chemical biology", "medicinal chemistry", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "toxicology", "urology", "cytotoxic", "palladium-based", "prostate", "epithelial", "cells"], "article_id"=>701349, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Engin Ulukaya", "Fiona M. Frame", "Buse Cevatemre", "Davide Pellacani", "Hannah Walker", "Vincent M. Mann", "Matthew S. Simms", "Michael J. Stower", "Veysel T. Yilmaz", "Norman J. Maitland"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064278.s001", "https://dx.doi.org/10.1371/journal.pone.0064278.s002", "https://dx.doi.org/10.1371/journal.pone.0064278.s003"], "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_Cytotoxic_Activity_of_a_Novel_Palladium_Based_Compound_on_Prostate_Cell_Lines_Primary_Prostate_Epithelial_Cells_and_Prostate_Stem_Cells_/701349", "title"=>"Differential Cytotoxic Activity of a Novel Palladium-Based Compound on Prostate Cell Lines, Primary Prostate Epithelial Cells and Prostate Stem Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-05-10 00:22:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/1058643"], "description"=>"<p>(A) Palladium complex [PdCl(terpy)](sac)·2 H<sub>2</sub>O, (sac = saccharinate, and terpy = 2,2′:6′,2″-terpyridine). M = Palladium(II) (B) Cisplatin (C) Etoposide.</p>", "links"=>[], "tags"=>["Molecular cell biology", "chemical biology", "medicinal chemistry", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "toxicology", "urology"], "article_id"=>701339, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Engin Ulukaya", "Fiona M. Frame", "Buse Cevatemre", "Davide Pellacani", "Hannah Walker", "Vincent M. Mann", "Matthew S. Simms", "Michael J. Stower", "Veysel T. Yilmaz", "Norman J. Maitland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0064278.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chemical_structures_/701339", "title"=>"Chemical structures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-10 00:22:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/1058644"], "description"=>"<p>Anti-growth effect was measured by the MTS assay at 24 h, 48 h and 72 h. PNT1A, PNT2-C2, and BPH-1 have either normal tissue or benign prostatic hyperplasia tissue origin (Ai–iii), while PC-3, LNCaP and P4E6 cell lines have malignant origin (Bi–iii). IC<sub>50s</sub> are presented in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064278#pone-0064278-t003\" target=\"_blank\">Table 3</a>. Transformed graphs are presented in Supplementary <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064278#pone.0064278.s001\" target=\"_blank\">Figure S1</a>.</p>", "links"=>[], "tags"=>["Molecular cell biology", "chemical biology", "medicinal chemistry", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "toxicology", "urology", "pd"], "article_id"=>701340, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Engin Ulukaya", "Fiona M. Frame", "Buse Cevatemre", "Davide Pellacani", "Hannah Walker", "Vincent M. Mann", "Matthew S. Simms", "Michael J. Stower", "Veysel T. Yilmaz", "Norman J. Maitland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0064278.g002", "stats"=>{"downloads"=>4, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Anti_growth_effect_of_the_Pd_complex_on_cell_lines_/701340", "title"=>"Anti-growth effect of the Pd complex on cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-10 00:22:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1058645"], "description"=>"<p>Anti-growth effect was measured by the MTS assay at 72 h using cells derived from patients with (A) benign prostate hyperplasia, (B) prostate carcinoma with Gleason grade 6/7 and (C) prostate carcinoma with Gleason grade 8/9. IC<sub>50s</sub> are presented in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064278#pone-0064278-t004\" target=\"_blank\">Table 4</a>. Transformed graphs are presented in Supplementary <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064278#pone.0064278.s002\" target=\"_blank\">Figure S2</a>.</p>", "links"=>[], "tags"=>["Molecular cell biology", "chemical biology", "medicinal chemistry", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "toxicology", "urology", "pd"], "article_id"=>701341, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Engin Ulukaya", "Fiona M. Frame", "Buse Cevatemre", "Davide Pellacani", "Hannah Walker", "Vincent M. Mann", "Matthew S. Simms", "Michael J. Stower", "Veysel T. Yilmaz", "Norman J. Maitland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0064278.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Anti_growth_effect_of_the_Pd_complex_on_primary_cultures_/701341", "title"=>"Anti-growth effect of the Pd complex on primary cultures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-10 00:22:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1058646"], "description"=>"<p>(A) MTS assay and ATP assay were compared to assess anti-growth effect using small cells numbers. (B) Anti-growth effect was measured by the ATP assay using SCs, TA cells and CB cells derived from three patients with benign prostate hyperplasia (white-filled shapes) and five patients with prostate carcinoma (black-filled shapes). White bar represents the median value of all the samples.</p>", "links"=>[], "tags"=>["Molecular cell biology", "chemical biology", "medicinal chemistry", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "toxicology", "urology", "pd", "cancer", "cells"], "article_id"=>701342, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Engin Ulukaya", "Fiona M. Frame", "Buse Cevatemre", "Davide Pellacani", "Hannah Walker", "Vincent M. Mann", "Matthew S. Simms", "Michael J. Stower", "Veysel T. Yilmaz", "Norman J. Maitland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0064278.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Anti_growth_effect_of_the_Pd_complex_on_cancer_stem_cells_CSC_/701342", "title"=>"Anti-growth effect of the Pd complex on cancer stem cells (CSC).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-10 00:22:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1058647"], "description"=>"<p>(A) Primary cultures isolated from two patients with prostate carcinoma were assessed. Cells were stained and scored for nuclear foci indicative of DNA damage Representative examples of cells negative and positive for nuclear foci are shown. (B) Normal (PNT2-C2) and benign (BPH-1) cell lines, three cancer cell lines (P4E6, PC-3 and LNCaP) and (C) four primary cultures derived from patients with prostate carcinoma were treated with three concentrations of palladium complex or etoposide or cisplatin as control treatments. Cell cycle phase was measured using propidium iodide staining and flow cytometry analysis.</p>", "links"=>[], "tags"=>["Molecular cell biology", "chemical biology", "medicinal chemistry", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "toxicology", "urology", "pd"], "article_id"=>701343, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Engin Ulukaya", "Fiona M. Frame", "Buse Cevatemre", "Davide Pellacani", "Hannah Walker", "Vincent M. Mann", "Matthew S. Simms", "Michael J. Stower", "Veysel T. Yilmaz", "Norman J. Maitland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0064278.g005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DNA_damaging_effect_and_effect_on_Cell_Cycle_Status_of_Pd_complex_/701343", "title"=>"DNA-damaging effect and effect on Cell Cycle Status of Pd complex.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-10 00:22:23"}

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Relative Metric

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