Pifithrin-μ, an Inhibitor of Heat-Shock Protein 70, Can Increase the Antitumor Effects of Hyperthermia Against Human Prostate Cancer Cells
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{"title"=>"Pifithrin-μ, an inhibitor of heat-shock protein 70, can increase the antitumor effects of hyperthermia against human prostate cancer cells", "type"=>"journal", "authors"=>[{"first_name"=>"Kazumasa", "last_name"=>"Sekihara", "scopus_author_id"=>"56903957900"}, {"first_name"=>"Nanae", "last_name"=>"Harashima", "scopus_author_id"=>"6604041371"}, {"first_name"=>"Miki", "last_name"=>"Tongu", "scopus_author_id"=>"10539586200"}, {"first_name"=>"Yukihisa", "last_name"=>"Tamaki", "scopus_author_id"=>"55967162000"}, {"first_name"=>"Nobue", "last_name"=>"Uchida", "scopus_author_id"=>"57197638754"}, {"first_name"=>"Taisuke", "last_name"=>"Inomata", "scopus_author_id"=>"7102562772"}, {"first_name"=>"Mamoru", "last_name"=>"Harada", "scopus_author_id"=>"7402782312"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"24244355", "doi"=>"10.1371/journal.pone.0078772", "sgr"=>"84892185056", "isbn"=>"1932-6203", "scopus"=>"2-s2.0-84892185056", "issn"=>"19326203", "pui"=>"372334625"}, "id"=>"6f47a086-5335-3691-bd03-c0b73d5bf3e0", "abstract"=>"Hyperthermia (HT) improves the efficacy of anti-cancer radiotherapy and chemotherapy. However, HT also inevitably evokes stress responses and increases the expression of heat-shock proteins (HSPs) in cancer cells. Among the HSPs, HSP70 is known as a pro-survival protein. In this study, we investigated the sensitizing effect of pifithrin (PFT)-μ, a small molecule inhibitor of HSP70, when three human prostate cancer cell lines (LNCaP, PC-3, and DU-145) were treated with HT (43°C for 2 h). All cell lines constitutively expressed HSP70, and HT further increased its expression in LNCaP and DU-145. Knockdown of HSP70 with RNA interference decreased the viability and colony-forming ability of cancer cells. PFT-μ decreased the viabilities of all cell lines at one-tenth the dose of Quercetin, a well-known HSP inhibitor. The combination therapy with suboptimal doses of PFT-μ and HT decreased the viability of cancer cells most effectively when PFT-μ was added immediately before HT, and this combination effect was abolished by pre-knockdown of HSP70, suggesting that the effect was mediated via HSP70 inhibition. The combination therapy induced cell death, partially caspase-dependent, and decreased proliferating cancer cells, with decreased expression of c-Myc and cyclin D1 and increased expression of p21(WAF1/Cip), indicating arrest of cell growth. Additionally, the combination therapy significantly decreased the colony-forming ability of cancer cells compared to therapy with either alone. Furthermore, in a xenograft mouse model, the combination therapy significantly inhibited PC-3 tumor growth. These findings suggest that PFT-μ can effectively enhance HT-induced antitumor effects via HSP70 inhibition by inducing cell death and arrest of cell growth, and that PFT-μ is a promising agent for use in combination with HT to treat prostate cancer.", "link"=>"http://www.mendeley.com/research/pifithrin%CE%BC-inhibitor-heatshock-protein-70-increase-antitumor-effects-hyperthermia-against-human-pros", "reader_count"=>27, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Librarian"=>2, "Student > Doctoral Student"=>3, "Researcher"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>9, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Librarian"=>2, "Student > Doctoral Student"=>3, "Researcher"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>9, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>9, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Physics and Astronomy"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Neuroscience"=>{"Neuroscience"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}}, "reader_count_by_country"=>{"Canada"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1281724"], "description"=>"<p>(<b>A</b>) Three prostate cancer cell lines were treated with HT (43°C for 2 h). Before and after 4, 8, 12, and 24 h, lysates were prepared and the expression of HSP70 was assessed by immunoblot. β-Actin was used as the control. The number represents the ratio of the expression of HSP70 to that of β-actin, which was evaluated by densitometry using ImageJ. (<b>B</b>) Three days after transfection of HSP70 siRNA or control siRNA, the expression of HSP70 was assessed by immunoblot. β-Actin was used as a control. (<b>C</b>) Three cell lines, which had been pre-transfected with HSP70 siRNA or control siRNA three days before, were cultured. After 48 h, cell viability (%) was determined using the WST-8 assay. The results are shown as the mean ± SD of three wells. * <i>P</i><0.05 (Student's <i>t</i>-test) (<b>D</b>) PC-3 and DU-145, which had been pre-transfected with HSP70 siRNA or control siRNA 2 days prior, were cultured for the colony-formation assay for 12 days. The results are shown as the mean ± SD of three wells. * <i>P</i><0.05 (Student's <i>t</i>-test) (<b>E</b>) LNCaP, which had been pre-transfected with HSP70 siRNA or control siRNA 2 days prior, were cultured for 12 days, and cell viability (%) was determined using the WST-8 assay. The results are shown as the mean ± SD of three wells. * <i>P</i><0.05 (Student's <i>t</i>-test).</p>", "links"=>[], "tags"=>["hsp70", "prostate", "cancer"], "article_id"=>851394, "categories"=>["Biological Sciences"], "users"=>["Kazumasa Sekihara", "Nanae Harashima", "Miki Tongu", "Yukihisa Tamaki", "Nobue Uchida", "Taisuke Inomata", "Mamoru Harada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078772.g001", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pro_survival_role_of_HSP70_in_human_prostate_cancer_cell_lines_/851394", "title"=>"Pro-survival role of HSP70 in human prostate cancer cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-14 04:20:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1281727"], "description"=>"<p>(<b>A</b>) Three cell lines were cultured with the indicated doses of Quercetin or PFT-μ. After 48 h, cell viability (%) was determined using the WST-8 assay. The results are shown as the mean ± SD of three wells. (<b>B</b>) Two days after transfection of HSP70 siRNA or control siRNA, the expression of HSP90 and HSP70 was assessed by immunoblot. The expression of these HSPs was also examined after the treatment with PFT-μ (5 µM). β-Actin was used as a control.</p>", "links"=>[], "tags"=>["quercetin", "viability", "prostate", "cancer"], "article_id"=>851397, "categories"=>["Biological Sciences"], "users"=>["Kazumasa Sekihara", "Nanae Harashima", "Miki Tongu", "Yukihisa Tamaki", "Nobue Uchida", "Taisuke Inomata", "Mamoru Harada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078772.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_Quercetin_and_PFT_956_on_the_viability_of_prostate_cancer_cells_/851397", "title"=>"Effects of Quercetin and PFT-μ on the viability of prostate cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-14 04:20:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1281728"], "description"=>"<p>(<b>A</b>) Three different protocols are shown. (<b>B</b>) Three cell lines were cultured with the indicated doses of PFT-μ based on three different protocols with HT (striped bar) or without HT (black bar). HT was performed at 43°C for 2 h. After 48 h, cell viability (%) was determined using the WST-8 assay. The results are shown as the mean ± SD of three wells. (<b>C</b>) Selected results are shown. The results are shown as the mean ± SD of three wells. * <i>P</i><0.05 (Student's <i>t</i>-test) (<b>D</b>) PC-3 and DU-145, which had been pre-transfected with HSP70 siRNA or control siRNA 2 days earlier, were culured with PFT-μ (5 µM) with/without HT (43°C for 2 h). After 48 h, cell viability (%) was determined using the WST-8 assay. The results are shown as the mean ± SD of three wells. * <i>P</i><0.05 (Student's <i>t</i>-test) N.S., not significant.</p>", "links"=>[], "tags"=>["ht", "prostate", "cancer"], "article_id"=>851398, "categories"=>["Biological Sciences"], "users"=>["Kazumasa Sekihara", "Nanae Harashima", "Miki Tongu", "Yukihisa Tamaki", "Nobue Uchida", "Taisuke Inomata", "Mamoru Harada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078772.g003", "stats"=>{"downloads"=>2, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_the_combination_of_HT_and_PFT_956_on_prostate_cancer_cells_/851398", "title"=>"Effects of the combination of HT and PFT-μ on prostate cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-14 04:20:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1281729"], "description"=>"<p>(<b>A</b>) Three cell lines were treated with HT (43°C for 2 h) and/or PFT-μ. After 48 h, flow cytometry was performed after staining with FITC-conjugated Annexin V and PI. A representative result is shown. The numbers represent the percentages of each subset. (<b>B</b>) LNCaP cells were treated with both HT and PFT-μ (5 µM) in the presence of z-VAD (20 µM) or control DMSO. After 48 h, flow cytometry was performed after staining with APC-conjugated Annexin V and PI. The numbers represent the percentages of each subset.</p>", "links"=>[], "tags"=>["ht"], "article_id"=>851399, "categories"=>["Biological Sciences"], "users"=>["Kazumasa Sekihara", "Nanae Harashima", "Miki Tongu", "Yukihisa Tamaki", "Nobue Uchida", "Taisuke Inomata", "Mamoru Harada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078772.g004", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cancer_cell_death_after_combination_therapy_with_HT_and_PFT_956_/851399", "title"=>"Cancer cell death after combination therapy with HT and PFT-μ.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-14 04:20:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1281730"], "description"=>"<p>(<b>A</b>) Three cell lines were treated with or without HT (43°C for 2 h) and PFT-μ (5 µM) for 2 days. During the last 5 h for LNCaP, 90 min for PC-3, and 3 h for DU-145, cells were cultured with BrdU (10 µM). Then, harvested cells were stained with FITC-conjugated anti-BrdU antibody and 7AAD, and flow cytometry was performed. Numbers represent the percentages of each subset. (<b>B</b>) Three cell lines were treated with either or both of HT and PFT-μ (5 µM) for 2 days, and the expression levels of c-Myc, cyclin D1, and p21<sup>WAF1/Cip</sup> protein were determined by immunoblot. β-Actin and α-tubulin were used as controls.</p>", "links"=>[], "tags"=>["ht", "arrested", "prostate", "cancer"], "article_id"=>851400, "categories"=>["Biological Sciences"], "users"=>["Kazumasa Sekihara", "Nanae Harashima", "Miki Tongu", "Yukihisa Tamaki", "Nobue Uchida", "Taisuke Inomata", "Mamoru Harada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078772.g005", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Combination_therapy_with_HT_and_PFT_956_arrested_the_growth_of_prostate_cancer_cells_/851400", "title"=>"Combination therapy with HT and PFT-μ arrested the growth of prostate cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-14 04:20:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1281731"], "description"=>"<p>(<b>A</b>) PC-3 and DU-145 cells were cultured for 14 days and their colony-formation capacities were determined. The results are shown as the mean ± SD of three wells. * <i>P</i><0.05 (Student's <i>t</i>-test) (<b>B</b>) LNCaP cells were cultured for 12 days, and viability (%) was determined using the WST-8 assay. The results are shown as the mean ± SD of three wells. * <i>P</i><0.05 (Student's <i>t</i>-test).</p>", "links"=>[], "tags"=>["ht", "colony-forming", "cancer"], "article_id"=>851401, "categories"=>["Biological Sciences"], "users"=>["Kazumasa Sekihara", "Nanae Harashima", "Miki Tongu", "Yukihisa Tamaki", "Nobue Uchida", "Taisuke Inomata", "Mamoru Harada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078772.g006", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Combination_therapy_with_HT_and_PFT_956_decreased_the_colony_forming_ability_of_cancer_cells_/851401", "title"=>"Combination therapy with HT and PFT-μ decreased the colony-forming ability of cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-14 04:20:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1281732"], "description"=>"<p>BALB <i>nu/nu</i> male mice were inoculated in the right footpad with 1×10<sup>6</sup> PC-3 cells with Matrigel. On day 15, the mice were pooled and divided into four groups. Each group contained six mice. On days 0 and 4 after grouping, the PC-3-bearing mice were locally injected with PFT-μ (100 µg in 50 µl) and/or treated with HT (43°C for 30 min). Arrows represent the day of treatment. As a vehicle control, 50 µl of DMSO were injected. HT was performed 1 h after the local injection of PFT-μ. Thereafter, the tumor size, the product of two perpendicular diameters (<b>A, B</b>), and the footpad thickness (<b>C, D</b>) were measured twice weekly. The results are shown as the mean ± SD of six mice. *<i>P</i><0.05 ** <i>P</i><0.01 (Dunnett test) N.S., not significant.</p>", "links"=>[], "tags"=>["antitumor", "ht", "xenograft"], "article_id"=>851402, "categories"=>["Biological Sciences"], "users"=>["Kazumasa Sekihara", "Nanae Harashima", "Miki Tongu", "Yukihisa Tamaki", "Nobue Uchida", "Taisuke Inomata", "Mamoru Harada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078772.g007", "stats"=>{"downloads"=>4, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_antitumor_effects_of_PFT_and_HT_in_a_xenograft_mouse_model_/851402", "title"=>"<i>In vivo</i> antitumor effects of PFT-μ and HT in a xenograft mouse model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-14 04:20:34"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"17", "full-text"=>"17", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"20", "full-text"=>"23", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[266, 468, 593, 703, 804, 903, 993, 1084, 1171, 1256, 1339, 1422, 1492]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[272, 472, 600, 713, 815, 911, 1004, 1094, 1185, 1273, 1358, 1441]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Medicine and health sciences/Oncology", "average_usage"=>[249, 468, 599, 718, 820, 920, 1008, 1093, 1181, 1281, 1357, 1444, 1517]}, {"subject_area"=>"/Medicine and health sciences/Urology", "average_usage"=>[264, 490, 621, 739, 833, 927, 1020, 1102, 1204, 1282, 1349, 1432, 1504]}]}
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