Natural Product Celastrol Destabilizes Tubulin Heterodimer and Facilitates Mitotic Cell Death Triggered by Microtubule-Targeting Anti-Cancer Drugs
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Natural product Celastrol destabilizes tubulin heterodimer and facilitates mitotic cell death triggered by microtubule-targeting anti-cancer drugs.", "type"=>"journal", "authors"=>[{"first_name"=>"Hakryul", "last_name"=>"Jo"}, {"first_name"=>"Fabien", "last_name"=>"Loison"}, {"first_name"=>"Hidenori", "last_name"=>"Hattori"}, {"first_name"=>"Leslie E", "last_name"=>"Silberstein"}, {"first_name"=>"Hongtao", "last_name"=>"Yu"}, {"first_name"=>"Hongbo R", "last_name"=>"Luo"}], "year"=>2010, "source"=>"PloS one", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0010318", "sgr"=>"77956397168", "issn"=>"1932-6203", "scopus"=>"2-s2.0-77956397168", "pui"=>"359494231", "pmid"=>"20428237"}, "keywords"=>["Antineoplastic Agents", "Antineoplastic Agents: pharmacology", "Antineoplastic Combined Chemotherapy Protocols", "Antineoplastic Combined Chemotherapy Protocols: ph", "Apoptosis", "Apoptosis: drug effects", "Biological Agents", "Biological Agents: therapeutic use", "Cells", "Cultured", "Drug Resistance", "Drug Synergism", "HeLa Cells", "Humans", "Microtubules", "Microtubules: drug effects", "Mitosis", "Neoplasm", "Neutrophils", "Neutrophils: cytology", "Protein Multimerization", "Protein Multimerization: drug effects", "Protein Stability", "Protein Stability: drug effects", "Triterpenes", "Triterpenes: pharmacology", "Triterpenes: therapeutic use", "Tubulin", "Tubulin: chemistry", "Tubulin: drug effects"], "id"=>"92a04656-3c12-3b61-943c-242f2a231899", "abstract"=>"BACKGROUND: Microtubule drugs are effective anti-cancer agents, primarily due to their ability to induce mitotic arrest and subsequent cell death. However, some cancer cells are intrinsically resistant or acquire a resistance. Lack of apoptosis following mitotic arrest is thought to contribute to drug resistance that limits the efficacy of the microtubule-targeting anti-cancer drugs. Genetic or pharmacological agents that selectively facilitate the apoptosis of mitotic arrested cells present opportunities to strengthen the therapeutic efficacy.\\n\\nMETHODOLOGY AND PRINCIPAL FINDINGS: We report a natural product Celastrol targets tubulin and facilitates mitotic cell death caused by microtubule drugs. First, in a small molecule screening effort, we identify Celastrol as an inhibitor of neutrophil chemotaxis. Subsequent time-lapse imaging analyses reveal that inhibition of microtubule-mediated cellular processes, including cell migration and mitotic chromosome alignment, is the earliest events affected by Celastrol. Disorganization, not depolymerization, of mitotic spindles appears responsible for mitotic defects. Celastrol directly affects the biochemical properties of tubulin heterodimer in vitro and reduces its protein level in vivo. At the cellular level, Celastrol induces a synergistic apoptosis when combined with conventional microtubule-targeting drugs and manifests an efficacy toward Taxol-resistant cancer cells. Finally, by time-lapse imaging and tracking of microtubule drug-treated cells, we show that Celastrol preferentially induces apoptosis of mitotic arrested cells in a caspase-dependent manner. This selective effect is not due to inhibition of general cell survival pathways or mitotic kinases that have been shown to enhance microtubule drug-induced cell death.\\n\\nCONCLUSIONS AND SIGNIFICANCE: We provide evidence for new cellular pathways that, when perturbed, selectively induce the apoptosis of mitotic arrested cancer cells, identifying a potential new strategy to enhance the therapeutic efficacy of conventional microtubule-targeting anti-cancer drugs.", "link"=>"http://www.mendeley.com/research/natural-product-celastrol-destabilizes-tubulin-heterodimer-facilitates-mitotic-cell-death-triggered", "reader_count"=>13, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Student > Master"=>1, "Other"=>2, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Student > Master"=>1, "Other"=>2, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>4, "Design"=>1, "Chemistry"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}}, "reader_count_by_country"=>{"Iran"=>1}, "group_count"=>0}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/77956397168"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/77956397168?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77956397168&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=77956397168&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/77956397168", "dc:identifier"=>"SCOPUS_ID:77956397168", "eid"=>"2-s2.0-77956397168", "dc:title"=>"Natural product celastrol destabilizes tubulin heterodimer and facilitates mitotic cell death triggered by microtubule-targeting anti-cancer drugs", "dc:creator"=>"Jo H.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"5", "prism:issueIdentifier"=>"4", "prism:pageRange"=>nil, "prism:coverDate"=>"2010-01-01", "prism:coverDisplayDate"=>"2010", "prism:doi"=>"10.1371/journal.pone.0010318", "citedby-count"=>"30", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Harvard Medical School", "affiliation-city"=>"Boston", "affiliation-country"=>"United States"}], "pubmed-id"=>"20428237", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e10318", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0010318", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Wikipedia | Further Information

Counter

  • {"month"=>"4", "year"=>"2010", "pdf_views"=>"36", "xml_views"=>"2", "html_views"=>"158"}
  • {"month"=>"5", "year"=>"2010", "pdf_views"=>"59", "xml_views"=>"0", "html_views"=>"141"}
  • {"month"=>"6", "year"=>"2010", "pdf_views"=>"33", "xml_views"=>"1", "html_views"=>"114"}
  • {"month"=>"7", "year"=>"2010", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"90"}
  • {"month"=>"8", "year"=>"2010", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"79"}
  • {"month"=>"9", "year"=>"2010", "pdf_views"=>"22", "xml_views"=>"1", "html_views"=>"75"}
  • {"month"=>"10", "year"=>"2010", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"50"}
  • {"month"=>"11", "year"=>"2010", "pdf_views"=>"43", "xml_views"=>"0", "html_views"=>"86"}
  • {"month"=>"12", "year"=>"2010", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"49"}
  • {"month"=>"1", "year"=>"2011", "pdf_views"=>"12", "xml_views"=>"2", "html_views"=>"51"}
  • {"month"=>"2", "year"=>"2011", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"67"}
  • {"month"=>"3", "year"=>"2011", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"70"}
  • {"month"=>"4", "year"=>"2011", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"5", "year"=>"2011", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"61"}
  • {"month"=>"6", "year"=>"2011", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"42"}
  • {"month"=>"7", "year"=>"2011", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"8", "year"=>"2011", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"38"}
  • {"month"=>"9", "year"=>"2011", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"71"}
  • {"month"=>"10", "year"=>"2011", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"65"}
  • {"month"=>"11", "year"=>"2011", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"72"}
  • {"month"=>"12", "year"=>"2011", "pdf_views"=>"25", "xml_views"=>"0", "html_views"=>"74"}
  • {"month"=>"1", "year"=>"2012", "pdf_views"=>"22", "xml_views"=>"1", "html_views"=>"55"}
  • {"month"=>"2", "year"=>"2012", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"3", "year"=>"2012", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"4", "year"=>"2012", "pdf_views"=>"16", "xml_views"=>"1", "html_views"=>"59"}
  • {"month"=>"5", "year"=>"2012", "pdf_views"=>"20", "xml_views"=>"1", "html_views"=>"59"}
  • {"month"=>"6", "year"=>"2012", "pdf_views"=>"18", "xml_views"=>"1", "html_views"=>"58"}
  • {"month"=>"7", "year"=>"2012", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"52"}
  • {"month"=>"8", "year"=>"2012", "pdf_views"=>"8", "xml_views"=>"5", "html_views"=>"28"}
  • {"month"=>"9", "year"=>"2012", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"10", "year"=>"2012", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"38"}
  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"59"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"56"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"45"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"49"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"28"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"84"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"3", "html_views"=>"20"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"2", "html_views"=>"22"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"2", "xml_views"=>"2", "html_views"=>"12"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"24"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"26"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"2", "xml_views"=>"2", "html_views"=>"17"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"15"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"18"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"28"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"34", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"2", "html_views"=>"26"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"37"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"12"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"0", "xml_views"=>"1", "html_views"=>"7"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"1"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"0", "xml_views"=>"3", "html_views"=>"5"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"10"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"10"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"2"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/424135", "https://ndownloader.figshare.com/files/424164", "https://ndownloader.figshare.com/files/424192", "https://ndownloader.figshare.com/files/424221", "https://ndownloader.figshare.com/files/424245", "https://ndownloader.figshare.com/files/424280", "https://ndownloader.figshare.com/files/424310", "https://ndownloader.figshare.com/files/424337", "https://ndownloader.figshare.com/files/424366", "https://ndownloader.figshare.com/files/424414", "https://ndownloader.figshare.com/files/424441", "https://ndownloader.figshare.com/files/424474", "https://ndownloader.figshare.com/files/424507", "https://ndownloader.figshare.com/files/424530"], "description"=>"<div><h3>Background</h3><p>Microtubule drugs are effective anti-cancer agents, primarily due to their ability to induce mitotic arrest and subsequent cell death. However, some cancer cells are intrinsically resistant or acquire a resistance. Lack of apoptosis following mitotic arrest is thought to contribute to drug resistance that limits the efficacy of the microtubule-targeting anti-cancer drugs. Genetic or pharmacological agents that selectively facilitate the apoptosis of mitotic arrested cells present opportunities to strengthen the therapeutic efficacy.</p><h3>Methodology and Principal Findings</h3><p>We report a natural product Celastrol targets tubulin and facilitates mitotic cell death caused by microtubule drugs. First, in a small molecule screening effort, we identify Celastrol as an inhibitor of neutrophil chemotaxis. Subsequent time-lapse imaging analyses reveal that inhibition of microtubule-mediated cellular processes, including cell migration and mitotic chromosome alignment, is the earliest events affected by Celastrol. Disorganization, not depolymerization, of mitotic spindles appears responsible for mitotic defects. Celastrol directly affects the biochemical properties of tubulin heterodimer <em>in vitro</em> and reduces its protein level <em>in vivo</em>. At the cellular level, Celastrol induces a synergistic apoptosis when combined with conventional microtubule-targeting drugs and manifests an efficacy toward Taxol-resistant cancer cells. Finally, by time-lapse imaging and tracking of microtubule drug-treated cells, we show that Celastrol preferentially induces apoptosis of mitotic arrested cells in a caspase-dependent manner. This selective effect is not due to inhibition of general cell survival pathways or mitotic kinases that have been shown to enhance microtubule drug-induced cell death.</p><h3>Conclusions and Significance</h3><p>We provide evidence for new cellular pathways that, when perturbed, selectively induce the apoptosis of mitotic arrested cancer cells, identifying a potential new strategy to enhance the therapeutic efficacy of conventional microtubule-targeting anti-cancer drugs.</p></div>", "links"=>[], "tags"=>["celastrol", "destabilizes", "tubulin", "heterodimer", "facilitates", "mitotic", "triggered", "microtubule-targeting", "anti-cancer", "drugs"], "article_id"=>143746, "categories"=>["Medicine", "Cell Biology", "Cancer", "Pharmacology"], "users"=>["Hakryul Jo", "Fabien Loison", "Hidenori Hattori", "Leslie E. Silberstein", "Hongtao Yu", "Hongbo R. Luo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0010318.s001", "https://dx.doi.org/10.1371/journal.pone.0010318.s002", "https://dx.doi.org/10.1371/journal.pone.0010318.s003", "https://dx.doi.org/10.1371/journal.pone.0010318.s004", "https://dx.doi.org/10.1371/journal.pone.0010318.s005", "https://dx.doi.org/10.1371/journal.pone.0010318.s006", "https://dx.doi.org/10.1371/journal.pone.0010318.s007", "https://dx.doi.org/10.1371/journal.pone.0010318.s008", "https://dx.doi.org/10.1371/journal.pone.0010318.s009", "https://dx.doi.org/10.1371/journal.pone.0010318.s010", "https://dx.doi.org/10.1371/journal.pone.0010318.s011", "https://dx.doi.org/10.1371/journal.pone.0010318.s012", "https://dx.doi.org/10.1371/journal.pone.0010318.s013", "https://dx.doi.org/10.1371/journal.pone.0010318.s014"], "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Natural_Product_Celastrol_Destabilizes_Tubulin_Heterodimer_and_Facilitates_Mitotic_Cell_Death_Triggered_by_Microtubule_Targeting_Anti_Cancer_Drugs/143746", "title"=>"Natural Product Celastrol Destabilizes Tubulin Heterodimer and Facilitates Mitotic Cell Death Triggered by Microtubule-Targeting Anti-Cancer Drugs", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-04-23 01:02:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/853164"], "description"=>"<p>(<b>A</b>) HEK293 cells were treated with Celastrol (2 µM) for 1 hour before fixation and staining with DAPI. The mitotic cells were counted and scored according to their chromosomal morphology. The proportion of each mitotic stage over the total number of counted cells was presented. (<b>B</b>) HeLa cells were treated with Nocodazole (100 nM) for 6 hours. The arrested cells were collected by tapping the plate, washed in PBS, and replated in a serum free medium. After 15 minutes of attachment (time 0), each drug was added and incubated for 30 minutes before fixation and staining with DAPI. The average number of cells in each stage from the quadruplicates was shown. ‘ND’ indicates the non-mitotic or dead cells. (<b>C</b>) Hela cells over-expressing EGFP-H2B protein were treated with indicated drugs. Immediately following drug addition, the prophase cells were identified and the time-lapse images were taken every 5 minutes for 90 minutes. The magnified still images from the representative movies were shown. (<b>D</b>) The summary of time-lapse movies for mitotic chromosome alignment in C). The degree of mitotic progression of prophase cells in 60 minutes in the presence of each chemical was determined based on chromosomal shape, and was indicated by horizontal bar. Numbers indicate number of cells examined. The representative chromosomal shapes of control cells at different mitotic stages were shown in lower panel as a reference.</p>", "links"=>[], "tags"=>["inhibits", "mitotic", "progression", "chromosome"], "article_id"=>523621, "categories"=>["Medicine", "Cell Biology", "Cancer", "Pharmacology"], "users"=>["Hakryul Jo", "Fabien Loison", "Hidenori Hattori", "Leslie E. Silberstein", "Hongtao Yu", "Hongbo R. Luo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010318.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Celastrol_inhibits_mitotic_progression_and_chromosome_alignment_/523621", "title"=>"Celastrol inhibits mitotic progression and chromosome alignment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-04-23 01:00:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/853681"], "description"=>"<p>(<b>A</b>) The time-lapse images of Vinblastine-arrested cells treated with different chemicals. The magnified still images were shown for the clarity. The pre-arrested mitotic or interphase cells to die within 150 minutes were indicated by red and blue arrows, respectively. (<b>B</b>) Quantification of mitotic or non-mitotic cell death. The percentage of dying cells over total number of cells in mitotic or interphase state at time 0 was presented. (<b>C</b>) Celastrol did not inhibit Vinblastine-induced phosphorylation of CDK target proteins. Cells were treated with each drug for 1 hour or pre-treated with Vinblastine (100 nM) for 30 minutes followed by subsequent drug treatment for 1 hour. The whole cell lysate was analyzed with the phospho-CDKs substrate antibody, and the same blot was probed with the actin antibody for loading control.</p>", "links"=>[], "tags"=>["selectively", "kills", "mitotic", "arrested"], "article_id"=>524135, "categories"=>["Medicine", "Cell Biology", "Cancer", "Pharmacology"], "users"=>["Hakryul Jo", "Fabien Loison", "Hidenori Hattori", "Leslie E. Silberstein", "Hongtao Yu", "Hongbo R. Luo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010318.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Celastrol_selectively_kills_mitotic_arrested_cells_/524135", "title"=>"Celastrol selectively kills mitotic arrested cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-04-23 01:08:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/853499"], "description"=>"<p>(<b>A</b>) HEK293 cell lysates were incubated in the presence of the indicated amount of Celastrol or 18-beta GCA for 15 minutes prior to SDS-PAGE in non-reducing condition. The membrane was blotted with the alpha-tubulin (top) or beta-tubulin antibody (bottom). (<b>B</b>) The cell lysates from control HEK293 cells were prepared and equally divided into four different tubes, and immunoprecipitation was carried out with a polyclonal alpha-tubulin antibody in the presence of DMSO or indicated amounts of Celastrol. After SDS-PAGE, the immune complex was blotted with the mouse monoclonal antibody against the alpha-, beta-, or gamma-tubuln. The amount of alpha-tubulin (top panel) serves as a loading control. (<b>C</b>) The immunoprecipitation and Western blot was carried out as in B) in the presence of different chemicals. (<b>D</b>) HEK293 cells were treated with indicated amounts of Celastrol for 1 hour, and the whole cell lysates were analyzed for the indicated cellular proteins. The same lysates were blotted with the phospho-CDK substrate antibody (right panel).</p>", "links"=>[], "tags"=>["causes", "defects", "tubulin"], "article_id"=>523953, "categories"=>["Medicine", "Cell Biology", "Cancer", "Pharmacology"], "users"=>["Hakryul Jo", "Fabien Loison", "Hidenori Hattori", "Leslie E. Silberstein", "Hongtao Yu", "Hongbo R. Luo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010318.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Celastrol_causes_structural_defects_of_tubulin_in_vitro_and_reduces_its_level_in_vivo_/523953", "title"=>"Celastrol causes structural defects of tubulin <i>in vitro</i> and reduces its level <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-04-23 01:05:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/853313"], "description"=>"<p>The representative immunostaining of microtubule (alpha- tubulin) and centrosome (gamma-tubulin) of the interphase and spindle morphology of mitotic HeLa cells treated for 1 hour with the indicated drugs; Celastrol (4 µM), Vinblastine (10 nM), and Taxol (10 nM).</p>", "links"=>[], "tags"=>["disorganizes", "mitotic"], "article_id"=>523767, "categories"=>["Medicine", "Cell Biology", "Cancer", "Pharmacology"], "users"=>["Hakryul Jo", "Fabien Loison", "Hidenori Hattori", "Leslie E. Silberstein", "Hongtao Yu", "Hongbo R. Luo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010318.g003", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Celastrol_disorganizes_mitotic_spindles_/523767", "title"=>"Celastrol disorganizes mitotic spindles.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-04-23 01:02:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/853791"], "description"=>"<p>HeLa cells expressing EGFP-Histone H2B (HeLa-H2B) were arrested at mitotic phase by Vinblastine treatment, and the indicated amounts of each drug was added. The apoptotic death of only the ‘pre-arrested’ mitotic cells in 4 hours as identified by time-lapse movie was scored. ‘Vinblastine only’ indicates without addition of other drugs and ‘Celastrol only’ indicates its effect on normal mitotic cells (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010318#s2\" target=\"_blank\">Materials and Methods</a>).</p>", "links"=>[], "tags"=>["pharmacological", "agents", "mitotic"], "article_id"=>524248, "categories"=>["Medicine", "Cell Biology", "Cancer", "Pharmacology"], "users"=>["Hakryul Jo", "Fabien Loison", "Hidenori Hattori", "Leslie E. Silberstein", "Hongtao Yu", "Hongbo R. Luo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010318.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_pharmacological_agents_on_mitotic_cell_death_/524248", "title"=>"Effect of pharmacological agents on mitotic cell death.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-04-23 01:10:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/853597"], "description"=>"<p>(<b>A</b>) The multinuclei phenotype of Taxol-resistant HeLa cells expressing Histone H2B-EGFP. Arrows indicate the cells with the multiple nuclei, and approximately 50% of cells displayed this phenotype. (<b>B</b>) The bright field images of parental and Taxol-resistant cells treated with Taxol (20 nM) for 36 hour or Celastrol (4 µM) for 24 hours. The percentage of dead cells was quantified based on the nuclear morphology as determined by Histone H2B-EGFP, and cells with the fragmented nuclei were counted as dead cells (right panel). (<b>C</b>) The sensitivity of parental and Taxol-resistant cells toward Taxol or Celastrol. Each cell line was treated with the indicated amounts of Taxol for 36 hours or Celastrol for 24 hours, and the cell viability was determined by MTT assay. The relative activity with respect to vehicle alone (DMSO) was presented. (<b>D</b>) The parental and Taxol-resistant cells were treated with DMSO or Celastrol (4 µM) for 6 hours, and the cytosolic cell lysates were subjected to caspase activity assay. The relative caspase activity over DMSO treatment was presented.</p>", "links"=>[], "tags"=>["cancer", "cells", "celastrol-induced"], "article_id"=>524049, "categories"=>["Medicine", "Cell Biology", "Cancer", "Pharmacology"], "users"=>["Hakryul Jo", "Fabien Loison", "Hidenori Hattori", "Leslie E. Silberstein", "Hongtao Yu", "Hongbo R. Luo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010318.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Taxol_resistant_cancer_cells_remain_sensitive_to_Celastrol_induced_apoptosis_/524049", "title"=>"Taxol-resistant cancer cells remain sensitive to Celastrol-induced apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-04-23 01:07:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/853027"], "description"=>"<p>(<b>A–B</b>) Celastrol inhibits fMLP-induced neutrophil chemotaxis. (<b>A</b>) Freshly isolated human peripheral blood neutrophils were pre-treated with each chemical for 30 minutes, and then subjected to fMLP-mediated chemotaxis for 20 minutes using the EZtaxiscan. The first and the last images of the videos were shown for each drug. fMLP (100 nM), Celastrol (2 µM), 17AAG (4 µM), MG132 (10 µM), and Gedunin (20 µM) were used in the indicated combination. (<b>B</b>) Left panel is the quantification of the migrating speed upon each drug treatment. Right panel is the whole cell lysate assay of the proteasomal activity treated with each drug for 1 hour. The concentration of all chemicals was 5 µM. (<b>C–D</b>) Celastrol reduces epithelial cancer cell motility. (<b>C</b>) The confluent HeLa cells were scratched using a tip. After 10 minutes of recovery, each drug was added and the time-lapse images were taken every 15 minute for 150 minutes. The representative still images of the first (time 0) and the last (time 150) time points were shown. For the sample of “Celastrol-wash”, cells were pre-treated with Celastrol for 3 hour before scratching; and the time-lapse movie was taken in a drug-free medium. (<b>D</b>) Quantification of cell migration. The relative migration area over the control (DMSO-treated) was presented. * indicates p<0.05 by student T-test.</p>", "links"=>[], "tags"=>["inhibits"], "article_id"=>523485, "categories"=>["Medicine", "Cell Biology", "Cancer", "Pharmacology"], "users"=>["Hakryul Jo", "Fabien Loison", "Hidenori Hattori", "Leslie E. Silberstein", "Hongtao Yu", "Hongbo R. Luo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010318.g001", "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Celastrol_inhibits_cell_migration_/523485", "title"=>"Celastrol inhibits cell migration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-04-23 00:58:05"}

PMC Usage Stats | Further Information

  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"6", "full-text"=>"66", "unique-ip"=>"65", "pdf"=>"60", "year"=>"2010", "figure"=>"19", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"37", "year"=>"2010", "pdf"=>"34", "unique-ip"=>"37", "figure"=>"38", "scanned-summary"=>"0", "supp-data"=>"4"}
  • {"scanned-page-browse"=>"0", "month"=>"7", "cited-by"=>"1", "abstract"=>"3", "full-text"=>"38", "unique-ip"=>"39", "pdf"=>"22", "year"=>"2010", "figure"=>"22", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"8", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"23", "year"=>"2010", "pdf"=>"12", "unique-ip"=>"23", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"9", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"30", "unique-ip"=>"31", "pdf"=>"13", "year"=>"2010", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"3"}
  • {"month"=>"10", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"26", "year"=>"2010", "pdf"=>"23", "unique-ip"=>"25", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"4"}
  • {"scanned-page-browse"=>"0", "month"=>"11", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"14", "unique-ip"=>"18", "pdf"=>"9", "year"=>"2010", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"11", "year"=>"2010", "pdf"=>"6", "unique-ip"=>"13", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"6", "unique-ip"=>"8", "pdf"=>"4", "year"=>"2011", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"2"}
  • {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"19", "year"=>"2011", "pdf"=>"11", "unique-ip"=>"22", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"2"}
  • {"scanned-page-browse"=>"0", "month"=>"3", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"31", "unique-ip"=>"27", "pdf"=>"13", "year"=>"2011", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"1"}
  • {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"8", "year"=>"2011", "pdf"=>"8", "unique-ip"=>"10", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"7", "unique-ip"=>"9", "pdf"=>"2", "year"=>"2011", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"16", "year"=>"2011", "pdf"=>"9", "unique-ip"=>"18", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"7", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"12", "unique-ip"=>"12", "pdf"=>"9", "year"=>"2011", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"8", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"15", "year"=>"2011", "pdf"=>"7", "unique-ip"=>"17", "figure"=>"8", "scanned-summary"=>"0", "supp-data"=>"1"}
  • {"scanned-page-browse"=>"0", "month"=>"9", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"17", "unique-ip"=>"17", "pdf"=>"8", "year"=>"2011", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"10", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"21", "year"=>"2011", "pdf"=>"10", "unique-ip"=>"17", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"11", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"14", "unique-ip"=>"18", "pdf"=>"10", "year"=>"2011", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"5", "year"=>"2011", "pdf"=>"6", "unique-ip"=>"6", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"12", "unique-ip"=>"12", "pdf"=>"9", "year"=>"2012", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"8", "year"=>"2012", "pdf"=>"5", "unique-ip"=>"8", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"3", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"11", "unique-ip"=>"13", "pdf"=>"7", "year"=>"2012", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"11", "year"=>"2012", "pdf"=>"9", "unique-ip"=>"10", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"7", "unique-ip"=>"9", "pdf"=>"4", "year"=>"2012", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"4", "full-text"=>"10", "year"=>"2012", "pdf"=>"12", "unique-ip"=>"13", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"4", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"7", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"12", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"14", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"7", "full-text"=>"3", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"14", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"1", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"19", "full-text"=>"21", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"13", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"13", "full-text"=>"6", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"6", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"6", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"9", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"6", "full-text"=>"8", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"28", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"21", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"3", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"16", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"9", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"5", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"6", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"12", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2010-01-01T00:00:00Z", "end_date"=>"2010-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[265, 560, 722, 863, 978, 1083, 1172, 1261, 1345, 1428, 1488, 1559, 1630, 1701, 1764, 1840, 1899, 1965, 2028, 2088, 2150, 2211, 2270, 2348, 2410, 2461, 2531, 2598, 2645, 2719, 2793, 2870, 2923, 2974, 3020, 3080, 3142, 3198, 3259, 3351, 3418, 3471, 3527, 3581, 3637, 3706, 3761, 3817, 3872]}, {"subject_area"=>"/Biology and life sciences/Immunology", "average_usage"=>[266, 530, 683, 806, 930, 1032, 1122, 1207, 1292, 1362, 1433, 1495, 1565, 1621, 1680, 1737, 1792, 1851, 1901, 1967, 2022, 2075, 2150, 2203, 2250, 2314, 2367, 2416, 2472, 2531, 2603, 2651, 2707, 2756, 2800, 2877, 2936, 2986, 3036, 3083, 3131, 3191, 3253, 3313, 3376, 3437, 3496, 3556]}, {"subject_area"=>"/Medicine and health sciences/Pharmaceutics", "average_usage"=>[300, 609, 770, 884, 1008, 1176, 1286, 1371, 1441, 1511, 1585, 1669, 1740, 1853, 1941, 2038, 2145, 2232, 2279, 2348, 2410, 2510, 2601, 2682, 2761, 2834, 2899, 2946, 3007, 3072, 3143, 3203, 3253, 3319, 3372, 3443, 3529, 3596, 3691, 3750, 3806, 3896, 3986, 4107, 4183, 4244, 4333, 4441, 4503]}]}
Loading … Spinner
There are currently no alerts