Reevesioside A, a Cardenolide Glycoside, Induces Anticancer Activity against Human Hormone-Refractory Prostate Cancers through Suppression of c-myc Expression and Induction of G1 Arrest of the Cell Cycle
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{"title"=>"Reevesioside A, a cardenolide glycoside, induces anticancer activity against human hormone-refractory prostate cancers through suppression of c-myc expression and induction of G1 arrest of the cell cycle", "type"=>"journal", "authors"=>[{"first_name"=>"Wohn Jenn", "last_name"=>"Leu", "scopus_author_id"=>"55853769800"}, {"first_name"=>"Hsun Shuo", "last_name"=>"Chang", "scopus_author_id"=>"57095223400"}, {"first_name"=>"She Hung", "last_name"=>"Chan", "scopus_author_id"=>"55853868200"}, {"first_name"=>"Jui Ling", "last_name"=>"Hsu", "scopus_author_id"=>"15841636700"}, {"first_name"=>"Chia Chun", "last_name"=>"Yu", "scopus_author_id"=>"41262835800"}, {"first_name"=>"Lih Ching", "last_name"=>"Hsu", "scopus_author_id"=>"25823231000"}, {"first_name"=>"Ih Sheng", "last_name"=>"Chen", "scopus_author_id"=>"7402043578"}, {"first_name"=>"Jih Hwa", "last_name"=>"Guh", "scopus_author_id"=>"57137905200"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84900325252", "pmid"=>"24475272", "sgr"=>"84900325252", "doi"=>"10.1371/journal.pone.0087323", "issn"=>"19326203", "pui"=>"373059139"}, "id"=>"8bce0139-1f0c-391e-81ba-e8c7a3dc75ac", "abstract"=>"In the past decade, there has been a profound increase in the number of studies revealing that cardenolide glycosides display inhibitory activity on the growth of human cancer cells. The use of potential cardenolide glycosides may be a worthwhile approach in anticancer research. Reevesioside A, a cardenolide glycoside isolated from the root of Reevesia formosana, displayed potent anti-proliferative activity against human hormone-refractory prostate cancers. A good correlation (r² = 0.98) between the expression of Na⁺/K⁺-ATPase α₃ subunit and anti-proliferative activity suggested the critical role of the α₃ subunit. Reevesioside A induced G1 arrest of the cell cycle and subsequent apoptosis in a thymidine block-mediated synchronization model. The data were supported by the down-regulation of several related cell cycle regulators, including cyclin D1, cyclin E and CDC25A. Reevesioside A also caused a profound decrease of RB phosphorylation, leading to an increased association between RB and E2F1 and the subsequent suppression of E2F1 activity. The protein and mRNA levels of c-myc, which can activate expression of many downstream cell cycle regulators, were dramatically inhibited by reevesioside A. Transient transfection of c-myc inhibited the down-regulation of both cyclin D1 and cyclin E protein expression to reevesioside A action, suggesting that c-myc functioned as an upstream regulator. Flow cytometric analysis of JC-1 staining demonstrated that reevesioside A also induced the significant loss of mitochondrial membrane potential. In summary, the data suggest that reevesioside A inhibits c-myc expression and down-regulates the expression of CDC25A, cyclin D1 and cyclin E, leading to a profound decrease of RB phosphorylation. G1 arrest is, therefore, induced through E2F1 suppression. Consequently, reevesioside A causes mitochondrial damage and an ultimate apoptosis in human hormone-refractory prostate cancer cells.", "link"=>"http://www.mendeley.com/research/reevesioside-cardenolide-glycoside-induces-anticancer-activity-against-human-hormonerefractory-prost", "reader_count"=>13, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>4, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>4, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>3, "Chemistry"=>1, "Energy"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Energy"=>{"Energy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Poland"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1362178"], "description"=>"<div><p>In the past decade, there has been a profound increase in the number of studies revealing that cardenolide glycosides display inhibitory activity on the growth of human cancer cells. The use of potential cardenolide glycosides may be a worthwhile approach in anticancer research. Reevesioside A, a cardenolide glycoside isolated from the root of <i>Reevesia formosana</i>, displayed potent anti-proliferative activity against human hormone-refractory prostate cancers. A good correlation (r<sup>2</sup> = 0.98) between the expression of Na<sup>+</sup>/K<sup>+</sup>-ATPase α<sub>3</sub> subunit and anti-proliferative activity suggested the critical role of the α<sub>3</sub> subunit. Reevesioside A induced G1 arrest of the cell cycle and subsequent apoptosis in a thymidine block-mediated synchronization model. The data were supported by the down-regulation of several related cell cycle regulators, including cyclin D1, cyclin E and CDC25A. Reevesioside A also caused a profound decrease of RB phosphorylation, leading to an increased association between RB and E2F1 and the subsequent suppression of E2F1 activity. The protein and mRNA levels of c-myc, which can activate expression of many downstream cell cycle regulators, were dramatically inhibited by reevesioside A. Transient transfection of c-myc inhibited the down-regulation of both cyclin D1 and cyclin E protein expression to reevesioside A action, suggesting that c-myc functioned as an upstream regulator. Flow cytometric analysis of JC-1 staining demonstrated that reevesioside A also induced the significant loss of mitochondrial membrane potential. In summary, the data suggest that reevesioside A inhibits c-myc expression and down-regulates the expression of CDC25A, cyclin D1 and cyclin E, leading to a profound decrease of RB phosphorylation. G1 arrest is, therefore, induced through E2F1 suppression. Consequently, reevesioside A causes mitochondrial damage and an ultimate apoptosis in human hormone-refractory prostate cancer cells.</p></div>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "Small molecules", "biotechnology", "Non-clinical medicine", "oncology", "Cancer treatment", "Complementary and alternative medicine", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "urology", "Prostate diseases", "cardenolide", "anticancer", "hormone-refractory", "prostate", "cancers", "suppression", "c-myc", "induction", "g1"], "article_id"=>914555, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Wohn-Jenn Leu", "Hsun-Shuo Chang", "She-Hung Chan", "Jui-Ling Hsu", "Chia-Chun Yu", "Lih-Ching Hsu", "Ih-Sheng Chen", "Jih-Hwa Guh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087323", "stats"=>{"downloads"=>6, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reevesioside_A_a_Cardenolide_Glycoside_Induces_Anticancer_Activity_against_Human_Hormone_Refractory_Prostate_Cancers_through_Suppression_of_c_myc_Expression_and_Induction_of_G1_Arrest_of_the_Cell_Cycle_/914555", "title"=>"Reevesioside A, a Cardenolide Glycoside, Induces Anticancer Activity against Human Hormone-Refractory Prostate Cancers through Suppression of c-myc Expression and Induction of G1 Arrest of the Cell Cycle", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-27 03:50:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1362163"], "description"=>"<p>PC-3 cells were incubated in the absence or presence of reevesioside A (50 nM) for the indicated times. Cells were incubated with JC-1 for the detection of Δψ<sub>m</sub> using flow cytometric analysis. The data are expressed as mean±SEM of three independent experiments. * <i>P</i><0.05 and *** <i>P</i><0.001 compared with the control.</p>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "Small molecules", "biotechnology", "Non-clinical medicine", "oncology", "Cancer treatment", "Complementary and alternative medicine", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "urology", "Prostate diseases", "reevesioside", "mitochondrial", "membrane"], "article_id"=>914540, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Wohn-Jenn Leu", "Hsun-Shuo Chang", "She-Hung Chan", "Jui-Ling Hsu", "Chia-Chun Yu", "Lih-Ching Hsu", "Ih-Sheng Chen", "Jih-Hwa Guh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087323.g004", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_reevesioside_A_on_mitochondrial_membrane_potential_m_/914540", "title"=>"Effect of reevesioside A on mitochondrial membrane potential (Δψ<sub>m</sub>).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-27 03:50:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1362158"], "description"=>"<p>(A) Synchronization of PC-3 cells was performed by thymidine block as described in the Materials and Methods section. Then, the cells were released in the absence (upper panel) or presence of 50 nM reevesioside A for the indicated times. Data are representative of five independent experiments. (B) DU-145 cells were incubated in serum-free medium for 48 hours (starvation) and then, 10% FBS was added in the absence or presence of reevesioside A for 18 hours. The cells were harvested for the detection of cell cycle population by flow cytometric analysis. Quantitative data are expressed as mean±SEM of five (A) or three (B) independent experiments. * <i>P</i><0.05, ** <i>P</i><0.01 and *** <i>P</i><0.001 compared with the respective control.</p>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "Small molecules", "biotechnology", "Non-clinical medicine", "oncology", "Cancer treatment", "Complementary and alternative medicine", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "urology", "Prostate diseases", "reevesioside", "cell-cycle"], "article_id"=>914535, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Wohn-Jenn Leu", "Hsun-Shuo Chang", "She-Hung Chan", "Jui-Ling Hsu", "Chia-Chun Yu", "Lih-Ching Hsu", "Ih-Sheng Chen", "Jih-Hwa Guh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087323.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_reevesioside_A_on_cell_cycle_progression_/914535", "title"=>"Effect of reevesioside A on cell-cycle progression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-27 03:50:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1362172"], "description"=>"<p>(A) PC-3 cells were incubated in the absence or presence of reevesioside A (50 nM) for various times. The cells were harvested and lysed for the detection of the indicated protein by Western blot analysis. The expression was quantified using the computerized image analysis system ImageQuant (Amersham Biosciences). The data are expressed as mean±SEM of three independent experiments. *** <i>P</i><0.001 compared with 100% control. (B) PC-3 cells were incubated in the absence or presence of reevesioside A (50 nM) for the indicated times. The cells were harvested for the determination of mRNA expression by RT-PCR. (C) PC-3 cells were transfected with the indicated plasmid. The cells were treated without or with reevesioside A (50 nM) for 6 hours. After treatment, the cells were harvested and lysed for the detection of the indicated protein by Western blot analysis.</p>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "Small molecules", "biotechnology", "Non-clinical medicine", "oncology", "Cancer treatment", "Complementary and alternative medicine", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "urology", "Prostate diseases"], "article_id"=>914549, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Wohn-Jenn Leu", "Hsun-Shuo Chang", "She-Hung Chan", "Jui-Ling Hsu", "Chia-Chun Yu", "Lih-Ching Hsu", "Ih-Sheng Chen", "Jih-Hwa Guh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087323.g006", "stats"=>{"downloads"=>3, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Determination_of_functional_involvement_of_c_myc_/914549", "title"=>"Determination of functional involvement of c-myc.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-27 03:50:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1362166"], "description"=>"<p>(A) PC-3 cells were incubated in the absence or presence of reevesioside A (50 nM) for various times. The cells were harvested and lysed for the detection of the indicated protein by Western blot analysis. (B) PC-3 cells were transfected with the indicated plasmid. Then, the cells were treated without or with reevesioside A (50 nM) for 24 hours. After treatment, the cells were harvested and lysed for the detection of the indicated protein by Western blot analysis. The expression was quantified using the computerized image analysis system ImageQuant (Amersham Biosciences). The data are expressed as mean±SEM of three independent experiments. * <i>P</i><0.05 and ** <i>P</i><0.01 compared with 100% control. WT-Akt, wild type Akt; CA-Akt, constitutively active Akt.</p>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "Small molecules", "biotechnology", "Non-clinical medicine", "oncology", "Cancer treatment", "Complementary and alternative medicine", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "urology", "Prostate diseases"], "article_id"=>914543, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Wohn-Jenn Leu", "Hsun-Shuo Chang", "She-Hung Chan", "Jui-Ling Hsu", "Chia-Chun Yu", "Lih-Ching Hsu", "Ih-Sheng Chen", "Jih-Hwa Guh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087323.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Determination_of_functional_involvement_of_Akt_/914543", "title"=>"Determination of functional involvement of Akt.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-27 03:50:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1362176"], "description"=>"<p>(A) The expression of Na<sup>+</sup>/K<sup>+</sup>-ATPase α<sub>3</sub> subunit was detected using Western blot analysis. The anti-proliferative IC<sub>50</sub> values were determined using SRB assays except for HL-60 cells by MTT assays. (B) PC-3 cells were incubated in the absence or presence of reevesioside A (50 nM) for the indicated times. After the treatment, the cells were harvested for the detection of intracellular Ca<sup>2+</sup> levels using flow cytometric analysis of the staining with fluo-3 AM. Data are expressed as mean±SEM of three independent experiments. * <i>P</i><0.05 compared with the control.</p>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "Small molecules", "biotechnology", "Non-clinical medicine", "oncology", "Cancer treatment", "Complementary and alternative medicine", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "urology", "Prostate diseases", "subunit", "anti-proliferative"], "article_id"=>914553, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Wohn-Jenn Leu", "Hsun-Shuo Chang", "She-Hung Chan", "Jui-Ling Hsu", "Chia-Chun Yu", "Lih-Ching Hsu", "Ih-Sheng Chen", "Jih-Hwa Guh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087323.g007", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlation_between_Na_K_ATPase_945_3_subunit_and_anti_proliferative_activity_/914553", "title"=>"Correlation between Na<sup>+</sup>/K<sup>+</sup>-ATPase α<sub>3</sub> subunit and anti-proliferative activity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-27 03:50:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1362161"], "description"=>"<p>(A) PC-3 cells were incubated in the absence or presence of reevesioside A (50 nM) for various times. Cells were harvested and lysed for the detection of the indicated protein expression by Western blot analysis. The expression was quantified using the computerized image analysis system ImageQuant (Amersham Biosciences). The data are expressed as mean±SEM of three to five independent experiments. * <i>P</i><0.05, ** <i>P</i><0.01 and *** <i>P</i><0.001 compared with 100% control. (B) After the treatment, the cells were harvested for immunoprecipitation assay. The protein expression was detected by Western blot analysis. Data are representative of three independent experiments.</p>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "Small molecules", "biotechnology", "Non-clinical medicine", "oncology", "Cancer treatment", "Complementary and alternative medicine", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "urology", "Prostate diseases", "reevesioside"], "article_id"=>914538, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Wohn-Jenn Leu", "Hsun-Shuo Chang", "She-Hung Chan", "Jui-Ling Hsu", "Chia-Chun Yu", "Lih-Ching Hsu", "Ih-Sheng Chen", "Jih-Hwa Guh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087323.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_reevesioside_A_on_the_expression_of_several_cell_cycle_regulators_/914538", "title"=>"Effect of reevesioside A on the expression of several cell cycle regulators.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-27 03:50:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1362154"], "description"=>"<p>Chemical structure of reevesioside A (A). The graded concentrations of reevesioside A were added to PC-3 and DU-145 cells for 48 hours (A) or a single concentration (50 nM) was added for 48 hours (B) or the indicated times (C). After the treatment, the cells were observed by microscopic examination (B) or the cells were fixed and stained for SRB assay (A) or labeled with CFSE for flow cytometric analysis. Data are expressed as mean±SEM of three to five determinations. ** <i>P</i><0.01 and *** <i>P</i><0.001 compared with the respective control. Arrowhead, cell apoptosis; star, cell differentiation; <i>bar</i>, 50 µm.</p>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "Small molecules", "biotechnology", "Non-clinical medicine", "oncology", "Cancer treatment", "Complementary and alternative medicine", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Basic cancer research", "urology", "Prostate diseases", "reevesioside"], "article_id"=>914533, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Wohn-Jenn Leu", "Hsun-Shuo Chang", "She-Hung Chan", "Jui-Ling Hsu", "Chia-Chun Yu", "Lih-Ching Hsu", "Ih-Sheng Chen", "Jih-Hwa Guh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087323.g001", "stats"=>{"downloads"=>0, "page_views"=>69, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_reevesioside_A_on_cell_proliferation_/914533", "title"=>"Effect of reevesioside A on cell proliferation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-27 03:50:26"}

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Relative Metric

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