EGCG Enhances Cisplatin Sensitivity by Regulating Expression of the Copper and Cisplatin Influx Transporter CTR1 in Ovary Cancer
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{"title"=>"EGCG enhances Cisplatin sensitivity by regulating expression of the copper and cisplatin influx transporter CTR1 in ovary cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Xuemin", "last_name"=>"Wang", "scopus_author_id"=>"56092244600"}, {"first_name"=>"Pan", "last_name"=>"Jiang", "scopus_author_id"=>"56080131400"}, {"first_name"=>"Pengqi", "last_name"=>"Wang", "scopus_author_id"=>"56079608300"}, {"first_name"=>"Chung S.", "last_name"=>"Yang", "scopus_author_id"=>"7407026280"}, {"first_name"=>"Xuerong", "last_name"=>"Wang", "scopus_author_id"=>"37361602000"}, {"first_name"=>"Qing", "last_name"=>"Feng", "scopus_author_id"=>"55913521800"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84957879716", "doi"=>"10.1371/journal.pone.0125402", "pui"=>"608141924", "pmid"=>"25927922", "scopus"=>"2-s2.0-84957879716", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"9f04a922-06f2-3e9a-97e8-5402fdf4987c", "abstract"=>"Cisplatin is one of the first-line platinum-based chemotherapeutic agents for treatment of many types of cancer, including ovary cancer. CTR1 (copper transporter 1), a transmembrane solute carrier transporter, has previously been shown to increase the cellular uptake and sensitivity of cisplatin. It is hypothesized that increased CTR1 expression would enhance the sensitivity of cancer cells to cisplatin (cDDP). The present study demonstrates for the first time that (-)-epigallocatechin-3-gallate (EGCG), a major polyphenol from green tea, can enhance CTR1 mRNA and protein expression in ovarian cancer cells and xenograft mice. EGCG inhibits the rapid degradation of CTR1 induced by cDDP. The combination of EGCG and cDDP increases the accumulation of cDDP and DNA-Pt adducts, and subsequently enhances the sensitivity of ovarian cancer SKOV3 and OVCAR3 cells to the chemotherapeutic agent. In the OVCAR3 ovarian cancer xenograft nude mice model, the combination of the lower concentration of cDDP and EGCG strongly repressed the tumor growth and exhibited protective effect on the nephrotoxicity induced by cisplatin. Overall, these findings uncover a novel chemotherapy mechanism of EGCG as an adjuvant for the treatment of ovarian cancer.", "link"=>"http://www.mendeley.com/research/egcg-enhances-cisplatin-sensitivity-regulating-expression-copper-cisplatin-influx-transporter-ctr1-o", "reader_count"=>25, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>3, "Researcher"=>2, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>3, "Researcher"=>2, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Germany"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2046825"], "description"=>"<p>(A) Effect of EGCG on ovary cancer cells survival fraction. OVCAR3 and SKOV3 cells were treated with the indicated concentrations of EGCG for 24 h, then followed by MTT assay to detect cell the survival fraction. (B) Effect of the combination of EGCG and cDDP on cell survival fraction. The cells were treated with indicated concentration of cDDP alone, or in combination with the EGCG (10 μM, shown as E10), and followed by MTT assay. (C) EGCG in combination with cDDP repressed colony formation. OVCAR3 cells were treated with 10 μM of EGCG alone or in combination of 10 μM of cDDP for 48 h. When the colonies formed two weeks later, colony formation assay was carried out. (D) The combination of EGCG and cDDP on cells apoptosis, Hoechst 33258 staining was used to detect apoptosis caused by the indicated treatments. (*<i>P</i><0.05, **<i>P</i><0.01)</p>", "links"=>[], "tags"=>["cisplatin", "cddp", "OVCAR 3 cells", "Ovary Cancer Cisplatin", "cancer cells", "sensitivity", "EGCG Enhances Cisplatin Sensitivity", "CTR 1 expression", "Cisplatin Influx Transporter CTR 1", "cancer SKOV 3", "transmembrane solute carrier transporter", "CTR 1 mRNA", "CTR 1", "novel chemotherapy mechanism"], "article_id"=>1399841, "categories"=>["Biological Sciences"], "users"=>["Xuemin Wang", "Pan Jiang", "Pengqi Wang", "Chung S. Yang", "Xuerong Wang", "Qing Feng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0125402.g001", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_EGCG_on_the_sensitivity_of_the_ovarian_cancer_to_cDDP_/1399841", "title"=>"Effect of EGCG on the sensitivity of the ovarian cancer to cDDP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-30 03:50:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2046826"], "description"=>"<p>OVCAR3 cells were treated with/without 10μM EGCG and 30 μMcDDP for 4 h, and then followed by ICP-MC assay. (A) Whole-cell Pt accumulation. (B) DNA-Pt adducts accumulation. (**<i>P</i><0.01)</p>", "links"=>[], "tags"=>["cisplatin", "cddp", "OVCAR 3 cells", "Ovary Cancer Cisplatin", "cancer cells", "sensitivity", "EGCG Enhances Cisplatin Sensitivity", "CTR 1 expression", "Cisplatin Influx Transporter CTR 1", "cancer SKOV 3", "transmembrane solute carrier transporter", "CTR 1 mRNA", "CTR 1", "novel chemotherapy mechanism"], "article_id"=>1399842, "categories"=>["Biological Sciences"], "users"=>["Xuemin Wang", "Pan Jiang", "Pengqi Wang", "Chung S. Yang", "Xuerong Wang", "Qing Feng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0125402.g002", "stats"=>{"downloads"=>4, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_EGCG_on_Pt_and_DNA_Pt_adducts_accumulation_in_the_cells_/1399842", "title"=>"Effects of EGCG on Pt and DNA-Pt adducts accumulation in the cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-30 03:50:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2046827"], "description"=>"<p>(A) Effect of EGCG on mRNA expression of CTR1, CTR2, ATP7A and ATP7B. After OVCAR3 cells were treated with indicated concentrations of EGCG for 24h, RT-PCR and qPCR were carried out to measure the CTR1 mRNA expression. (B and C) Effect of EGCG on CTR1 protein expression in OVCAR3 and SKOV3 cells. The cells were treated with 10 μM EGCG for 24 h, then followed by western blot analysis. The bands were quantified with Image J software. (*<i>P</i><0.05, **<i>P</i><0.01)</p>", "links"=>[], "tags"=>["cisplatin", "cddp", "OVCAR 3 cells", "Ovary Cancer Cisplatin", "cancer cells", "sensitivity", "EGCG Enhances Cisplatin Sensitivity", "CTR 1 expression", "Cisplatin Influx Transporter CTR 1", "cancer SKOV 3", "transmembrane solute carrier transporter", "CTR 1 mRNA", "CTR 1", "novel chemotherapy mechanism"], "article_id"=>1399843, "categories"=>["Biological Sciences"], "users"=>["Xuemin Wang", "Pan Jiang", "Pengqi Wang", "Chung S. Yang", "Xuerong Wang", "Qing Feng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0125402.g003", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_EGCG_on_the_expression_of_copper_transporters_/1399843", "title"=>"Effect of EGCG on the expression of copper transporters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-30 03:50:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2046828"], "description"=>"<p>(A) Effect of knock-down of CTR1 on the sensitivity of ovary cancer cells to cDDP. OVCAR3 cells were transfected with three company sythetic si-RNAs or siRNA control and the western blost analysis showed si-RNA 3 exhibiting the best effect. After transfected with si-RNA3 or siRNA control, OVCAR3 and SKOV3 cells were treated with cDDP at various doses for 48 h and the cell survival fraction was detected by MTT assay. (B) Embryonic kidney HEK-293 cells were tranfected with human CTR1 si-RNA3 or siRNA control. Then the cells were exposed by indicated doses of cDDP for 48 h and the cell survival fraction was detected by MTT assay. (*<i>P</i><0.05).</p>", "links"=>[], "tags"=>["cisplatin", "cddp", "OVCAR 3 cells", "Ovary Cancer Cisplatin", "cancer cells", "sensitivity", "EGCG Enhances Cisplatin Sensitivity", "CTR 1 expression", "Cisplatin Influx Transporter CTR 1", "cancer SKOV 3", "transmembrane solute carrier transporter", "CTR 1 mRNA", "CTR 1", "novel chemotherapy mechanism"], "article_id"=>1399844, "categories"=>["Biological Sciences"], "users"=>["Xuemin Wang", "Pan Jiang", "Pengqi Wang", "Chung S. Yang", "Xuerong Wang", "Qing Feng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0125402.g004", "stats"=>{"downloads"=>2, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_knock_down_of_CTR1_on_the_sensitivity_of_cells_to_cDDP_/1399844", "title"=>"Effect of knock-down of CTR1 on the sensitivity of cells to cDDP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-30 03:50:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2046829"], "description"=>"<p>(A, B) The effect of cDDP on the expression of CTR1 in OVCAR3 and SKOV3 cells. The cells were treated with 10 μM cDDP for the indicated time and CTR1 protein expression were detected by western blot analysis. (C)The effect of MG132 on the degradation of CTR1. After OVCAR3 cells were pretreated with 5 μM MG132 for 10h, the cells were incubation with 10 μM cDDP for 14 h. Then followed by western blot analysis. (D, E) The effect of EGCG on cDDP-trigged decrease of CTR1. The OVCAR3 and SKOV3 cells were treated with/without 10μM EGCG in the presence/absence of 10μMcDDP for 24 h. CTR1 protein expression was detected. The bands were quantified with Image J software. (*<i>P</i><0.05, **<i>P</i><0.01)</p>", "links"=>[], "tags"=>["cisplatin", "cddp", "OVCAR 3 cells", "Ovary Cancer Cisplatin", "cancer cells", "sensitivity", "EGCG Enhances Cisplatin Sensitivity", "CTR 1 expression", "Cisplatin Influx Transporter CTR 1", "cancer SKOV 3", "transmembrane solute carrier transporter", "CTR 1 mRNA", "CTR 1", "novel chemotherapy mechanism"], "article_id"=>1399845, "categories"=>["Biological Sciences"], "users"=>["Xuemin Wang", "Pan Jiang", "Pengqi Wang", "Chung S. Yang", "Xuerong Wang", "Qing Feng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0125402.g005", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_EGCG_inhibits_the_degredation_of_CTR1_induced_by_cDDP_/1399845", "title"=>"EGCG inhibits the degredation of CTR1 induced by cDDP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-30 03:50:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2046830"], "description"=>"<p>Four groups (control, EGCG, cDDP and EGCG+cDDP) were set up. Except there were 6 mice in control group, there were 8 mice for each of the other groups. The body weight (A) and the tumor size (A) were measured twice a week. (B) The mRNA expression of the CTR1 in tumor tissues was measured by RT-PCR and real qPCR. (C) The expression of CTR1 in tumor tissue was assessed by western blotting. (D) The expression of CTR1 in kidney tissue was measured by western blotting. The bands were quantified by Image J software. (*P<0.05, **P<0.01)</p>", "links"=>[], "tags"=>["cisplatin", "cddp", "OVCAR 3 cells", "Ovary Cancer Cisplatin", "cancer cells", "sensitivity", "EGCG Enhances Cisplatin Sensitivity", "CTR 1 expression", "Cisplatin Influx Transporter CTR 1", "cancer SKOV 3", "transmembrane solute carrier transporter", "CTR 1 mRNA", "CTR 1", "novel chemotherapy mechanism"], "article_id"=>1399846, "categories"=>["Biological Sciences"], "users"=>["Xuemin Wang", "Pan Jiang", "Pengqi Wang", "Chung S. Yang", "Xuerong Wang", "Qing Feng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0125402.g006", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_EGCG_enhances_the_efficacy_of_cDDP_on_tumor_responsiveness_and_attenuates_the_nephrotoxicity_induced_by_cDDP_in_vivo_/1399846", "title"=>"EGCG enhances the efficacy of cDDP on tumor responsiveness and attenuates the nephrotoxicity induced by cDDP in vivo.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-30 03:50:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2046831"], "description"=>"<p>Values are presented as mean ± SD. The “n” means mice number.</p><p>* values differ significantly from control (<i>p<0</i>.<i>05</i>)</p><p>Changes of kidney weight and kidney injury indicators in various groups.</p>", "links"=>[], "tags"=>["cisplatin", "cddp", "OVCAR 3 cells", "Ovary Cancer Cisplatin", "cancer cells", "sensitivity", "EGCG Enhances Cisplatin Sensitivity", "CTR 1 expression", "Cisplatin Influx Transporter CTR 1", "cancer SKOV 3", "transmembrane solute carrier transporter", "CTR 1 mRNA", "CTR 1", "novel chemotherapy mechanism"], "article_id"=>1399847, "categories"=>["Biological Sciences"], "users"=>["Xuemin Wang", "Pan Jiang", "Pengqi Wang", "Chung S. Yang", "Xuerong Wang", "Qing Feng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0125402.t001", "stats"=>{"downloads"=>8, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_of_kidney_weight_and_kidney_injury_indicators_in_various_groups_/1399847", "title"=>"Changes of kidney weight and kidney injury indicators in various groups.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-30 03:50:46"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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