Activation of p38/JNK Pathway Is Responsible for Embelin Induced Apoptosis in Lung Cancer Cells: Transitional Role of Reactive Oxygen Species
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{"title"=>"Activation of p38/JNK pathway is responsible for embelin induced apoptosis in lung cancer cells: Transitional role of reactive oxygen species", "type"=>"journal", "authors"=>[{"first_name"=>"Deepa R.", "last_name"=>"Avisetti", "scopus_author_id"=>"56134956400"}, {"first_name"=>"K. Suresh", "last_name"=>"Babu", "scopus_author_id"=>"35847096500"}, {"first_name"=>"Shasi V.", "last_name"=>"Kalivendi", "scopus_author_id"=>"35563161800"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"372974107", "doi"=>"10.1371/journal.pone.0087050", "pmid"=>"24466324", "issn"=>"19326203", "scopus"=>"2-s2.0-84899567691", "sgr"=>"84899567691"}, "id"=>"50f5448d-742f-3147-bba6-5d18b2fed6c1", "abstract"=>"The natural product embelin has been demonstrated to possess a wide range of therapeutic properties, however, the mechanisms by which it exerts anticancer effects are not yet clear. By monitoring the molecular changes associated during early apoptotic phase, we have identified the crucial role of oxidative stress induced MAP kinase signalling as a predominant mechanism for its anticancer effects. Treatment of A549 lung cancer cells with embelin resulted in the enhancement of phospho-p38 and phospho-JNK levels as early as 4h. Pretreatment of cells with specific inhibitors of p38 (PD169316) and JNK (SP600125) abrogated embelin-induced caspase-3 activation. Studies employing embelin in the presence or absence of specific MAP kinase inhibitors indicated that the observed changes in phosphorylation levels of p38, JNK and ERK 1/2 are solely due to embelin and not because of cross-talk between MAP kinases. Reactive oxygen species (ROS) play a crucial role in embelin induced alterations in MAP kinase phosphorylation and apoptosis as pretreatment of cells with FeTMPyP mitigated this effect. The observed changes are not due to the inhibitory effect of embelin on XIAP as cells treated with SMAC-N7-Ant peptide, a specific inhibitor of XIAP's BIR3 domain did not mimic embelin induced apoptotic effects. The findings of the present study clearly indicate the crucial role of p38 and JNK pathways in embelin induced apoptosis and provide us with new clues for improving its therapeutic efficacy.", "link"=>"http://www.mendeley.com/research/activation-p38jnk-pathway-responsible-embelin-induced-apoptosis-lung-cancer-cells-transitional-role", "reader_count"=>15, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1355458"], "description"=>"<p>A549 cells were pre-treated with or without U0126 (5 µM), PD169316 (5 µM), SP600125 (5 µM) for 1h followed by embelin (15 µM) for 4h. Total and phosphorylated levels of ERK 1/2, p38, JNK 1/2 and tubulin (loading control) were detected by Western blotting as described in the “Materials and Methods” section.</p>", "links"=>[], "tags"=>["Biochemistry", "Small molecules", "genetics", "genomics", "Genome expression analysis", "Molecular cell biology", "Signal transduction", "Signaling cascades", "ERK signaling cascade", "MAPK signaling cascades", "Signaling in cellular processes", "Apoptotic signaling", "Redox signaling", "Cellular stress responses", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "induced", "kinase", "phosphorylation", "cross-talk"], "article_id"=>907936, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Deepa R. Avisetti", "K. Suresh Babu", "Shasi V. Kalivendi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087050.g005", "stats"=>{"downloads"=>5, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Embelin_induced_changes_in_MAP_kinase_phosphorylation_does_not_involve_cross_talk_between_MAP_kinases_/907936", "title"=>"Embelin induced changes in MAP kinase phosphorylation does not involve cross-talk between MAP kinases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-22 03:06:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1355467"], "description"=>"<p>(<b>A</b>) A549 cells were pretreated with or without FeTMPyP (10 µM) or NAC (10 mM) for 1h followed by embelin (15 µM) for 4h and ROS generation was detected by DCF staining as described in the “Materials and Methods” section. Cellular fluorescence was captured using an Olympus–IX71 inverted fluorescence microscope equipped with FITC filter settings. (<b>B</b>) Mean fluorescence intensity from three different fields of view were obtained using ImageJ software. * indicates p<0.05 as compared with control and # indicates p<0.05 as compared with embelin treated cells.</p>", "links"=>[], "tags"=>["Biochemistry", "Small molecules", "genetics", "genomics", "Genome expression analysis", "Molecular cell biology", "Signal transduction", "Signaling cascades", "ERK signaling cascade", "MAPK signaling cascades", "Signaling in cellular processes", "Apoptotic signaling", "Redox signaling", "Cellular stress responses", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "abrogate", "embelin", "induced", "oxidative"], "article_id"=>907945, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Deepa R. Avisetti", "K. Suresh Babu", "Shasi V. Kalivendi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087050.g006", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antioxidants_abrogate_embelin_induced_oxidative_stress_/907945", "title"=>"Antioxidants abrogate embelin induced oxidative stress.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-22 03:06:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1355441"], "description"=>"<p>(<b>A</b>) A549 cells were treated with 15 µM embelin for different time intervals. Following the termination of treatments, caspase-3 activity was measured as indicated in the “Materials and Methods” section. (<b>B</b>) A549 cells were treated with 15 µM embelin for 4h and stained with Annexin-V/FITC and propidium iodide as described in the “Materials and Methods” section. Fluorescence images were captured using an Olympus–IX71 inverted fluorescence microscope equipped with FITC and rhodamine filter settings. Representative images from three different fields of view are shown. (<b>C</b>) Cells were treated with an XIAP inhibitor, SMAC-N7-Ant peptide (100 µM) for 8h. Later, caspase-3 and -9- activities were measured using the tetra-peptide substrates as described under “Materials and Methods” section. For both (<b>A</b>) and (<b>C</b>) data presented are the mean ± SD of three separate experiments. **indicates p<0.01 and * indicates p<0.05 as compared with controls.</p>", "links"=>[], "tags"=>["Biochemistry", "Small molecules", "genetics", "genomics", "Genome expression analysis", "Molecular cell biology", "Signal transduction", "Signaling cascades", "ERK signaling cascade", "MAPK signaling cascades", "Signaling in cellular processes", "Apoptotic signaling", "Redox signaling", "Cellular stress responses", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "embelin", "smac-n7-ant", "peptide", "cellular"], "article_id"=>907913, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Deepa R. Avisetti", "K. Suresh Babu", "Shasi V. Kalivendi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087050.g002", "stats"=>{"downloads"=>2, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_embelin_and_SMAC_N7_Ant_peptide_on_cellular_apoptosis_/907913", "title"=>"Effect of embelin and SMAC-N7-Ant peptide on cellular apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-22 03:06:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1355448"], "description"=>"<p>(<b>A</b>) A549 cells were treated with 15 µM embelin for 4 and 8h. Total as well as phosphorylated ERK 1/2, p38, JNK 1/2 and tubulin (loading control) levels were measured by Western blot as described in the “Materials and Methods” section. (<b>B</b>) Normalized values of the band intensities obtained by densitometric analysis of the data from (<b>A</b>). (<b>C</b>) Caspase-3 activity in cells pre-treated with or without U0126 (5 µM), PD169316 (5 µM), SP600125 (5 µM) for 1h followed by embelin (15 µM) for 4h. Control values are normalized to 1 and the data indicated are the mean ± SD of three separate experiments. * indicates p<0.05 as compared with control and # indicates p<0.05 as compared with embelin treated cells.</p>", "links"=>[], "tags"=>["Biochemistry", "Small molecules", "genetics", "genomics", "Genome expression analysis", "Molecular cell biology", "Signal transduction", "Signaling cascades", "ERK signaling cascade", "MAPK signaling cascades", "Signaling in cellular processes", "Apoptotic signaling", "Redox signaling", "Cellular stress responses", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "kinases", "embelin", "induced"], "article_id"=>907927, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Deepa R. Avisetti", "K. Suresh Babu", "Shasi V. Kalivendi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087050.g004", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Role_of_MAP_kinases_in_embelin_induced_apoptosis_/907927", "title"=>"Role of MAP kinases in embelin induced apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-22 03:06:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1355470"], "description"=>"<p>A549 cells were pre-treated with or without the antioxidant FeTMPyP (10 µM) for 1h followed by embelin (15 µM) treatment for 4h. (<b>A</b>) Cellular levels of total and phosphorylated ERK 1/2, p38, JNK 1/2 and tubulin were detected by Western blot followed by chemiluminescence detection as described under “Materials and Methods” section. (<b>B</b>) Under similar experimental conditions as (<b>A</b>), cellular caspase-3 activity was measured as described under “Materials and Methods” section. Data presented are the mean ± SD of three separate experiments. <b>*</b> indicates p<0.01 as compared to control and <b>#</b> indicates p<0.05 as compared to embelin treated cells.</p>", "links"=>[], "tags"=>["Biochemistry", "Small molecules", "genetics", "genomics", "Genome expression analysis", "Molecular cell biology", "Signal transduction", "Signaling cascades", "ERK signaling cascade", "MAPK signaling cascades", "Signaling in cellular processes", "Apoptotic signaling", "Redox signaling", "Cellular stress responses", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "induced", "oxidative", "regulates", "mapk", "mediated"], "article_id"=>907948, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Deepa R. Avisetti", "K. Suresh Babu", "Shasi V. Kalivendi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087050.g007", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Embelin_induced_oxidative_stress_regulates_MAPK_mediated_apoptosis_/907948", "title"=>"Embelin induced oxidative stress regulates MAPK mediated apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-22 03:06:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1355431"], "description"=>"<p>(<b>A</b>) Structure of Embelin (<b>B</b>) Cells were treated with embelin for 48h and following the termination of incubation, cell viability was measured by sulphorhodamine B assay and IC<sub>50</sub> values were calculated as mentioned in the “Materials and Methods” section. Data shown are mean ± SD of three separate experiments. * indicates p<0.01as compared with controls.</p>", "links"=>[], "tags"=>["Biochemistry", "Small molecules", "genetics", "genomics", "Genome expression analysis", "Molecular cell biology", "Signal transduction", "Signaling cascades", "ERK signaling cascade", "MAPK signaling cascades", "Signaling in cellular processes", "Apoptotic signaling", "Redox signaling", "Cellular stress responses", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "embelin", "cancer"], "article_id"=>907902, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Deepa R. Avisetti", "K. Suresh Babu", "Shasi V. Kalivendi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087050.g001", "stats"=>{"downloads"=>4, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytotoxicity_of_embelin_in_cancer_and_normal_cell_lines_/907902", "title"=>"Cytotoxicity of embelin in cancer and normal cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-22 03:06:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1355442"], "description"=>"<p>A549 cells were treated with embelin (15 µM) for 4h. Microarray analysis was performed as described in “Materials and Methods” section. Genes that showed differential regulation by at least 2-fold with p<0.05 were classified based on functional category and pathways using GeneSpring GX and Genotypic Biointerpreter-Biological Analysis Software. Pathways that predominantly showed differential expression were (<b>A</b>) MAP Kinase pathway, (<b>B</b>) Cytokine-cytokine receptor interaction and (<b>C</b>) p53 pathway. The data has been submitted to GEO database with accession number GSE50545.</p>", "links"=>[], "tags"=>["Biochemistry", "Small molecules", "genetics", "genomics", "Genome expression analysis", "Molecular cell biology", "Signal transduction", "Signaling cascades", "ERK signaling cascade", "MAPK signaling cascades", "Signaling in cellular processes", "Apoptotic signaling", "Redox signaling", "Cellular stress responses", "oncology", "Cancer treatment", "Chemotherapy and drug treatment", "pathway", "induced"], "article_id"=>907919, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Deepa R. Avisetti", "K. Suresh Babu", "Shasi V. Kalivendi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087050.g003", "stats"=>{"downloads"=>5, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Alterations_in_pathway_based_gene_expression_profile_induced_by_embelin_/907919", "title"=>"Alterations in pathway based gene expression profile induced by embelin.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-22 03:06:17"}

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  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"7", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"3", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}

Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[291]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[282]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[286]}]}
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