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{"title"=>"Berberine radiosensitizes human esophageal cancer cells by downregulating homologous recombination repair protein RAD51", "type"=>"journal", "authors"=>[{"first_name"=>"Qiao", "last_name"=>"Liu", "scopus_author_id"=>"36238108000"}, {"first_name"=>"Haiyan", "last_name"=>"Jiang", "scopus_author_id"=>"54990950400"}, {"first_name"=>"Zhaojian", "last_name"=>"Liu", "scopus_author_id"=>"26024753400"}, {"first_name"=>"Yu", "last_name"=>"Wang", "scopus_author_id"=>"54992544500"}, {"first_name"=>"Minnan", "last_name"=>"Zhao", "scopus_author_id"=>"49562148300"}, {"first_name"=>"Chunyan", "last_name"=>"Hao", "scopus_author_id"=>"24070185900"}, {"first_name"=>"Shuai", "last_name"=>"Feng", "scopus_author_id"=>"49561335200"}, {"first_name"=>"Haiyang", "last_name"=>"Guo", "scopus_author_id"=>"37116836100"}, {"first_name"=>"Bing", "last_name"=>"Xu", "scopus_author_id"=>"57198894674"}, {"first_name"=>"Qifeng", "last_name"=>"Yang", "scopus_author_id"=>"7404076318"}, {"first_name"=>"Yaoqin", "last_name"=>"Gong", "scopus_author_id"=>"7402473493"}, {"first_name"=>"Changshun", "last_name"=>"Shao", "scopus_author_id"=>"7102817023"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-79961192394", "sgr"=>"79961192394", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0023427", "pmid"=>"21858113", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"362294546"}, "id"=>"1ec39d1d-475f-3e17-87ae-85918977f194", "abstract"=>"BACKGROUND: Esophageal squamous cell carcinomas (ESCC) have poor prognosis. While combined modality of chemotherapy and radiotherapy increases survival, most patients die within five years. Development of agents that confer cancer cell-specific chemo- and radiosensitivity may improve the therapy of ESCC. We here reported the discovery of berberine as a potent radiosensitizing agent on ESCC cells.\\n\\nPRINCIPAL FINDINGS: Berberine at low concentrations (<15 µM) substantially radiosensitized ESCC cells. X-ray induced DNA double-strand breaks (DSBs) persist longer in ESCC cells pretreated with berberine. Berberine pretreatment led to a significant downregulation of RAD51, a key player in homologous recombination repair, in ESCC cells, but not in non-malignant human cells. Downregulation of RAD51 by RNA interference similarly radiosensitized the cancer cells, and, conversely, introduction of exogenous RAD51 was able to significantly counteract the radiosensitizing effect of berberine, thus establishing RAD51 as a key determinant in radiation sensitivity. We also observed that RAD51 was commonly overexpressed in human ESCC tissues, suggesting that it is necessary to downregulate RAD51 to achieve high radio- or chemotherapeutic efficacy of ESCC in clinic, because overexpression of RAD51 is known to confer radio- and chemoresistance.\\n\\nCONCLUSIONS/SIGNIFICANCE: Berberine can effectively downregulate RAD51 in conferring radiosensitivity on esophageal cancer cells. Its clinical application as an adjuvant in chemotherapy and radiotherapy of esophageal cancers should be explored.", "link"=>"http://www.mendeley.com/research/berberine-radiosensitizes-human-esophageal-cancer-cells-downregulating-homologous-recombination-repa", "reader_count"=>24, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>9, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>4}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>9, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>4}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>5, "Business, Management and Accounting"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}}, "reader_count_by_country"=>{"United States"=>1, "Japan"=>1}, "group_count"=>0}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/748133"], "description"=>"<p>(A), Radiation enhances RAD51 expression in tumor cells. Cells were exposed to the indicated doses of radiation and collected 24 h later for immunoblot analysis. (B), Change of RAD51 protein levels in response to berberine and radiation. Cells were pretreated with berberine (15 µM) for 24 h before being irradiated with 6 Gy of X-rays. Cells were collected for immunoblot analysis at 24 h after irradiation. (C), Inhibition of radiation-induced RAD51 foci formation by berberine. Shown are immunofluorescence images of KYSE30 and KYSE450 cells stained with anti-RAD51 antibody after 24 h of pretreatment with berberine and at 24 h after irradiation with 6 Gy of X-rays. DAPI counterstaining showed the nuclei. (D), <i>RAD51</i> mRNA levels after pretreatment with berberine (15 µM) for 24 h (KYSE30) or 48 h (KYSE450) before irradiation with 6 Gy. Cells were collected for quantitative real-time PCR analysis of the RAD51/GAPDH mRNA ratios at 24 h after exposure to 6 Gy of X-rays. Immunoblots and mRNA expression values are representative of at least two independent experiments.</p>", "links"=>[], "tags"=>["rad51", "ir", "attenuated"], "article_id"=>418497, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Qiao Liu", "Haiyan Jiang", "Zhaojian Liu", "Yu Wang", "Minnan Zhao", "Chunyan Hao", "Shuai Feng", "Haiyang Guo", "Bing Xu", "Qifeng Yang", "Yaoqin Gong", "Changshun Shao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023427.g005", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Upregulation_of_RAD51_by_IR_can_be_attenuated_by_berberine_/418497", "title"=>"Upregulation of RAD51 by IR can be attenuated by berberine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:56:09"}
• {"files"=>["https://ndownloader.figshare.com/files/747751"], "description"=>"<p>(A), Radiosensitization by berberine by clonogenic cell survival assay. KYSE30 and KYSE450 cells were exposed to berberine (15 µM) or vehicle control (DMSO) for 24 and 48 h, respectively, before they were irradiated and plated. Human normal fibroblast cells were treated with berberine for 24 h and 48 h before they were exposed to X-rays. Data points are the averages of two independent experiments each plated in triplicate; bars, SE. (B), SF2 values following treatment with berberine. Decrease in the SF2 values indicates the radiosensitizing effects of berberine.</p>", "links"=>[], "tags"=>["esophageal", "cancer", "cells"], "article_id"=>418115, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Qiao Liu", "Haiyan Jiang", "Zhaojian Liu", "Yu Wang", "Minnan Zhao", "Chunyan Hao", "Shuai Feng", "Haiyang Guo", "Bing Xu", "Qifeng Yang", "Yaoqin Gong", "Changshun Shao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023427.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Radiosensitization_of_esophageal_cancer_cells_by_berberine_/418115", "title"=>"Radiosensitization of esophageal cancer cells by berberine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:53:33"}
• {"files"=>["https://ndownloader.figshare.com/files/748239"], "description"=>"<p>(A), Downregulation of RAD51 by siRNA. RAD51 protein levels were measured by Western blot. KYSE30 and KYSE450 cells were transfected with siRNA duplexes (200 nM) specific to <i>RAD51</i> or negative oligo in serum-free medium for 4 h, then replaced with complete medium for 24 h. Whole cell extracts were collected for western blot analysis using RAD51 antibodies. (B). Reduced formation of radiation-induced RAD51 foci in esophageal cancer cells in which <i>RAD51</i> was silenced by RNAi. Cells were exposed to 6 Gy of X-rays at 28 h following transfection with siRNA duplexes. (C), Effect of RAD51 knockdown on radiosensitivity of esophageal cancer cells as determined by clonogenic survival assay. (D), Western blot analysis of RAD51 protein in cancer cells that were transfected with pcDNA3.1 or pcDNA3.1B-mRAD51. The immunoblots shown are representative of two independent experiments with GAPDH serving as a protein loading control (KYSE30/KYSE450 parent cell line, KYSE30/KYSE450 (pcDNA3.1) cells stably transfected with pcDNA3.1, KYSE30/KYSE450 (mRAD51) cells stably transfected with pcDNA3.1B-mRAD51). (E), Effect of RAD51 overexpression on radiosensitivity of esophageal cancer cells as determined by clonogenic survival assay. The results for the cells transfected with the mRAD51 or pcDNA3.1 vector treated with berberine were compared (*P<0.01).</p>", "links"=>[], "tags"=>["determines", "radiosensitivity", "escc"], "article_id"=>418597, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Qiao Liu", "Haiyan Jiang", "Zhaojian Liu", "Yu Wang", "Minnan Zhao", "Chunyan Hao", "Shuai Feng", "Haiyang Guo", "Bing Xu", "Qifeng Yang", "Yaoqin Gong", "Changshun Shao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023427.g006", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RAD51_expression_level_determines_radiosensitivity_of_ESCC_cells_/418597", "title"=>"RAD51 expression level determines radiosensitivity of ESCC cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:56:44"}
• {"files"=>["https://ndownloader.figshare.com/files/748368"], "description"=>"<p>Images of showing different expression level and cellular distribution are shown. (A), absence of RAD51-specific staining (blue nuclei due to Mayer's Hemalum counterstaining). (B), low levels of RAD51 in the cytoplasm, but not in nuclei, of the invasive carcinoma cells. (C), intermediate levels of RAD51 in both the cytoplasm and nuclei of the invasive carcinoma cells. (D), high levels of RAD51 in the cytoplasm, but not in nuclei, of the invasive carcinoma cells. (E), high levels of nuclear RAD51 in the nuclei of invasive carcinoma cells. No cytoplasm staining is evident. (F), absence of RAD51 staining in normal esophageal tissue. Immunohistochemistry was done as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023427#s4\" target=\"_blank\">Materials and Methods</a>. All original images were captured at×400 magnification.</p>", "links"=>[], "tags"=>["up-regulated", "esophageal", "cancer"], "article_id"=>418727, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Qiao Liu", "Haiyan Jiang", "Zhaojian Liu", "Yu Wang", "Minnan Zhao", "Chunyan Hao", "Shuai Feng", "Haiyang Guo", "Bing Xu", "Qifeng Yang", "Yaoqin Gong", "Changshun Shao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023427.g007", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RAD51_is_up_regulated_in_human_esophageal_cancer_specimens_/418727", "title"=>"RAD51 is up-regulated in human esophageal cancer specimens.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:57:25"}
• {"files"=>["https://ndownloader.figshare.com/files/747652"], "description"=>"<p>(A), Effect of berberine on the viability of KYSE30, KYSE450 and HNF cells. Cell viability was assessed by MTT assay. Cells were treated with DMSO or the indicated concentrations of berberine for 24 h, 48 h and 72 h. Results were represented as mean ± SD from three independent experiments. (B), Cytotoxicity of berberine against KYSE30, KYSE450 and HNF cells represented by inhibitory concentrations IC50. (C), Measurement of apoptosis by Western blot analysis of caspase-3. KYSE30 and KYSE450 cells were treated with berberine for 24 h and 48 h, respectively. Paclitaxel-treated HL-60 and HeLa cells as positive control.</p>", "links"=>[], "tags"=>["berberine", "esophageal", "cancer"], "article_id"=>418000, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Qiao Liu", "Haiyan Jiang", "Zhaojian Liu", "Yu Wang", "Minnan Zhao", "Chunyan Hao", "Shuai Feng", "Haiyang Guo", "Bing Xu", "Qifeng Yang", "Yaoqin Gong", "Changshun Shao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023427.g001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Growth_inhibitory_effect_of_berberine_on_esophageal_cancer_cells_/418000", "title"=>"Growth-inhibitory effect of berberine on esophageal cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:52:53"}
• {"files"=>["https://ndownloader.figshare.com/files/748506"], "description"=>"<p>Lack of association between RAD51 levels and the clinicopathological parameters in ESCC specimens.</p>", "links"=>[], "tags"=>["rad51", "levels", "clinicopathological", "parameters", "escc"], "article_id"=>418866, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Qiao Liu", "Haiyan Jiang", "Zhaojian Liu", "Yu Wang", "Minnan Zhao", "Chunyan Hao", "Shuai Feng", "Haiyang Guo", "Bing Xu", "Qifeng Yang", "Yaoqin Gong", "Changshun Shao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023427.t001", "stats"=>{"downloads"=>8, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lack_of_association_between_RAD51_levels_and_the_clinicopathological_parameters_in_ESCC_specimens_/418866", "title"=>"Lack of association between RAD51 levels and the clinicopathological parameters in ESCC specimens.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 15:58:11"}
• {"files"=>["https://ndownloader.figshare.com/files/747902"], "description"=>"<p>(A), Immunofluorescence staining of γ-H2AX in KYSE30 cells. (B), Summary of γ-H2AX foci in KYSE30 cells at different time points following various treatments. (C), Summary of γ-H2AX foci in KYSE450 cells at different time points following various treatments. Columns, means of three independent experiments. Cells growing on coverslips in 6-well plates were exposed to berberine (15 µM) for 24, irradiated (0.5 Gy), and fixed at the specified time points for immunofluorescence analysis.</p>", "links"=>[], "tags"=>["pre-treatment", "led", "prolonged", "persistence", "ir-induced"], "article_id"=>418260, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Qiao Liu", "Haiyan Jiang", "Zhaojian Liu", "Yu Wang", "Minnan Zhao", "Chunyan Hao", "Shuai Feng", "Haiyang Guo", "Bing Xu", "Qifeng Yang", "Yaoqin Gong", "Changshun Shao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023427.g003", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Berberine_pre_treatment_led_to_a_prolonged_persistence_of_IR_induced_947_H2AX_foci_/418260", "title"=>"Berberine pre-treatment led to a prolonged persistence of IR-induced γ-H2AX foci.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:54:45"}
• {"files"=>["https://ndownloader.figshare.com/files/748016"], "description"=>"<p>(A), The levels of DNA repair proteins in esophageal cancer cells treated with berberine. Cells were treated with berberine at the indicated concentrations and for the indicated duration before cells were prepared for cell extracts. (B), Decrease in <i>RAD51</i> mRNA levels after berberine exposure. Cells were exposed to berberine (15 µM) for 24 h for KYSE30 cells (48 h for KYSE450 cells), and collected for quantitative real-time PCR analysis of the RAD51/GAPDH mRNA ratios. (C), <i>RAD51</i> promoter activity was suppressed by berberine in KYSE30 and KYSE450 cells. The pGL3-RAD51p luciferase (firefly) reporter plasmids were transiently transfected into human esophageal cancer cells. Four h later, the cells were treated with berberine for 24 h, and then assayed for luciferase activity. Firefly luciferase values were normalized to Renilla luciferase activity from a co-transfected pRL-SV40 control vector. Each value represents the mean SE for three independent experiments. Statistical analysis was performed using unpaired Student's <i>t test. *</i>, P<0.05 as compared with control values. (D), Lack of RAD51 downregulation in nonmalignant cells. Cells were exposed to berberine (15 µM) for the specified time period and collected for immunoblot analysis. (E), Downregulation of RAD51 in other types of cancer cells. Cells were exposed to the designated berberine concentration for 48 h and collected for immunoblot analysis. The immunoblots shown in A, D, and E are representative of at least two independent experiments with GAPDH serving as a protein loading control. C indicates cultures exposed to the vehicle control DMSO.</p>", "links"=>[], "tags"=>["downregulates", "rad51"], "article_id"=>418384, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Qiao Liu", "Haiyan Jiang", "Zhaojian Liu", "Yu Wang", "Minnan Zhao", "Chunyan Hao", "Shuai Feng", "Haiyang Guo", "Bing Xu", "Qifeng Yang", "Yaoqin Gong", "Changshun Shao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023427.g004", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Berberine_downregulates_RAD51_in_tumor_cells_/418384", "title"=>"Berberine downregulates RAD51 in tumor cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:55:28"}

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Relative Metric

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F1000Prime