Withania somnifera Water Extract as a Potential Candidate for Differentiation Based Therapy of Human Neuroblastomas
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{"title"=>"Withania somnifera Water Extract as a Potential Candidate for Differentiation Based Therapy of Human Neuroblastomas", "type"=>"journal", "authors"=>[{"first_name"=>"Hardeep", "last_name"=>"Kataria", "scopus_author_id"=>"56684924000"}, {"first_name"=>"Renu", "last_name"=>"Wadhwa", "scopus_author_id"=>"7006876025"}, {"first_name"=>"Sunil C.", "last_name"=>"Kaul", "scopus_author_id"=>"7403092602"}, {"first_name"=>"Gurcharan", "last_name"=>"Kaur", "scopus_author_id"=>"7103023716"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84873142408", "pui"=>"368246821", "doi"=>"10.1371/journal.pone.0055316", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84873142408", "pmid"=>"23383150"}, "id"=>"6dafc17a-82dc-383e-acd5-63492cf358ea", "abstract"=>"Neuroblastoma is an aggressive childhood disease of the sympathetic nervous system. Treatments are often ineffective and have serious side effects. Conventional therapy of neuroblastoma includes the differentiation agents. Unlike chemo-radiotherapy, differentiation therapy shows minimal side effects on normal cells, because normal non-malignant cells are already differentiated. Keeping in view the limited toxicity of Withania somnifera (Ashwagandha), the current study was aimed to investigate the efficacy of Ashwagandha water extract (ASH-WEX) for anti-proliferative potential in neuroblastoma and its underlying signalling mechanisms. ASH-WEX significantly reduced cell proliferation and induced cell differentiation as indicated by morphological changes and NF200 expression in human IMR-32 neuroblastoma cells. The induction of differentiation was accompanied by HSP70 and mortalin induction as well as pancytoplasmic translocation of the mortalin in ASH-WEX treated cells. Furthermore, the ASH-WEX treatment lead to induction of neural cell adhesion molecule (NCAM) expression and reduction in its polysialylation, thus elucidating its anti-migratory potential, which was also supported by downregulation of MMP 2 and 9 activity. ASH-WEX treatment led to cell cycle arrest at G0/G1 phase and increase in early apoptotic population. Modulation of cell cycle marker Cyclin D1, anti-apoptotic marker bcl-xl and Akt-P provide evidence that ASH-WEX may prove to be a promising phytotherapeutic intervention in neuroblatoma related malignancies.", "link"=>"http://www.mendeley.com/research/withania-somnifera-water-extract-potential-candidate-differentiation-based-therapy-human-neuroblasto", "reader_count"=>31, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>3, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>3, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>14, "Medicine and Dentistry"=>9, "Neuroscience"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Neuroscience"=>{"Neuroscience"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>14}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"India"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/480910"], "description"=>"<div><p>Neuroblastoma is an aggressive childhood disease of the sympathetic nervous system. Treatments are often ineffective and have serious side effects. Conventional therapy of neuroblastoma includes the differentiation agents. Unlike chemo-radiotherapy, differentiation therapy shows minimal side effects on normal cells, because normal non-malignant cells are already differentiated. Keeping in view the limited toxicity of <em>Withania somnifera</em> (Ashwagandha), the current study was aimed to investigate the efficacy of Ashwagandha water extract (ASH-WEX) for anti-proliferative potential in neuroblastoma and its underlying signalling mechanisms. ASH-WEX significantly reduced cell proliferation and induced cell differentiation as indicated by morphological changes and NF200 expression in human IMR-32 neuroblastoma cells. The induction of differentiation was accompanied by HSP70 and mortalin induction as well as pancytoplasmic translocation of the mortalin in ASH-WEX treated cells. Furthermore, the ASH-WEX treatment lead to induction of neural cell adhesion molecule (NCAM) expression and reduction in its polysialylation, thus elucidating its anti-migratory potential, which was also supported by downregulation of MMP 2 and 9 activity. ASH-WEX treatment led to cell cycle arrest at G0/G1 phase and increase in early apoptotic population. Modulation of cell cycle marker Cyclin D1, anti-apoptotic marker bcl-xl and Akt-P provide evidence that ASH-WEX may prove to be a promising phytotherapeutic intervention in neuroblatoma related malignancies.</p> </div>", "links"=>[], "tags"=>["extract", "differentiation", "based", "neuroblastomas"], "article_id"=>155227, "categories"=>["Cancer", "Cell Biology"], "users"=>["Hardeep Kataria", "Renu Wadhwa", "Sunil C. Kaul", "Gurcharan Kaur"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055316", "stats"=>{"downloads"=>1, "page_views"=>41, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Withania_somnifera_Water_Extract_as_a_Potential_Candidate_for_Differentiation_Based_Therapy_of_Human_Neuroblastomas__/155227", "title"=>"<em>Withania somnifera</em> Water Extract as a Potential Candidate for Differentiation Based Therapy of Human Neuroblastomas", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-31 01:27:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/497528"], "description"=>"<p>The relative intensity measurement of immunofluorescence is shown as histogram for HSP70 (b) and Mortalin (c). Representative Western blot hybridization signals for HSP70 (d) and Mortalin (e) from control and test samples and their relative intensity. Representative RT-PCR results for HSP70 and Mortalin mRNA in control and treated cells and their relative densitometry analysis represented by histograms. “*” represents the statistical significant (p<0.05) difference between control and ASH-WEX treated groups.</p>", "links"=>[], "tags"=>["mortalin", "ash-wex", "ra", "treated", "imr-32", "cultures"], "article_id"=>168035, "categories"=>["Cancer", "Cell Biology"], "users"=>["Hardeep Kataria", "Renu Wadhwa", "Sunil C. Kaul", "Gurcharan Kaur"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055316.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HSP70_and_Mortalin_expression_in_response_to_ASH_WEX_treatment_in_control_ASH_WEX_0_2_and_0_5_and_RA_treated_IMR_32_cultures_a_/168035", "title"=>"HSP70 and Mortalin expression in response to ASH-WEX treatment in control, ASH-WEX (0.2% and 0.5%) and RA treated IMR-32 cultures (a).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-31 02:13:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/497923"], "description"=>"<p>Representative Western blot hybridization signals for NCAM (b) and PSA-NCAM (c). Representative RT-PCR results for NCAM and PST mRNA in control and treated cells and their relative densitometry analysis represented by histograms. “*” represents the statistical significant (p<0.05) difference between control and ASH-WEX treated groups.</p>", "links"=>[], "tags"=>["psa-ncam", "ash-wex", "ra", "treated", "imr-32", "cultures"], "article_id"=>168436, "categories"=>["Cancer", "Cell Biology"], "users"=>["Hardeep Kataria", "Renu Wadhwa", "Sunil C. Kaul", "Gurcharan Kaur"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055316.g005", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NCAM_and_PSA_NCAM_expression_in_response_to_ASH_WEX_treatment_in_control_ASH_WEX_0_2_and_0_5_and_RA_treated_IMR_32_cultures_a_/168436", "title"=>"NCAM and PSA-NCAM expression in response to ASH-WEX treatment in control, ASH-WEX (0.2% and 0.5%) and RA treated IMR-32 cultures (a).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-31 02:20:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/497659"], "description"=>"<p>Relative intensity measurement of immunofluorescence is shown as histograms for Cyclin D1 (b), bcl-xl (c) and Akt-P (d). Representative Western blot hybridization signals for Cyclin D1, bcl-xl and Akt-P from control and test samples (0.5% ASH-WEX and RA treated cells) (e). mRNA expression analysis for Cyclin D1, bcl-xl and Akt-P was done and densometery results for intensity analysis are represented as histogram (f). “*” represents the statistical significant (p<0.05) difference between control and ASH-WEX treated groups.</p>", "links"=>[], "tags"=>["detection", "cyclin", "bcl-xl", "akt-p", "shown", "ra", "treated", "imr-32cells"], "article_id"=>168171, "categories"=>["Cancer", "Cell Biology"], "users"=>["Hardeep Kataria", "Renu Wadhwa", "Sunil C. Kaul", "Gurcharan Kaur"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055316.g003", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunofluorescence_detection_of_Cyclin_D1_bcl_xl_and_Akt_P_is_shown_in_control_0_2_and_0_5_ASH_WEX_RA_treated_IMR_32cells_a_/168171", "title"=>"Immunofluorescence detection of Cyclin D1, bcl-xl and Akt-P is shown in control, 0.2% and 0.5% ASH-WEX, RA treated IMR-32cells (a).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-31 02:16:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/498058"], "description"=>"<p>Images show the starting (0 h after scratch) and the end (24 h after scratch) point of the analysis. (b) Graph shows that the rate of IMR-32 migration in response to ASH-WEX treatment in comparison to untreated cells. Data are obtained from a set of scratch test analysis (N  = 3) and are expressed as means ± standard error. Representative MMP zymogram from control and treated samples and their densometery analysis is represented as histogram (c). mRNA expression for MMP2 and MMP9 was analyzed by RT-PCR. Relative percentage expression was expressed as histogram (d). “*” represents the statistical significant (p<0.05) difference between control and ASH-WEX treated groups.</p>", "links"=>[], "tags"=>["images", "ash-wex", "ra", "treated", "motility", "was", "wound-scratch"], "article_id"=>168569, "categories"=>["Cancer", "Cell Biology"], "users"=>["Hardeep Kataria", "Renu Wadhwa", "Sunil C. Kaul", "Gurcharan Kaur"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055316.g006", "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_phase_contrast_images_of_control_0_2_or_0_5_ASH_WEX_and_RA_treated_cells_in_which_motility_was_analyzed_by_Wound_scratch_test_a_/168569", "title"=>"Representative phase contrast images of control, 0.2% or 0,5% ASH-WEX and RA treated cells, in which motility was analyzed by Wound-scratch test (a).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-31 02:22:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/497396"], "description"=>"<p>Data are representative of three different experiments done in triplicates and expressed as mean ± S.E.M. (b) Phase contrast images of IMR-32, TGW, SH-SY5Y and Neuro-2a neurolastoma cells treated with 0.0% (Control), 0.2% and 0.5% ASH-WEX. (c) NF200 expression in response to ASH-WEX treatment in control, ASH-WEX (0.2% and 0.5%) and RA treated IMR-32 cultures. The relative intensity measurement of immunofluorescence is shown (d). (e) Representative Western blot hybridization signals for NF200 from control and test samples. (f) Representative RT-PCR results for NF200 mRNA in control and treated cells and their relative densitometry analysis represented by histograms. “*” represents the statistical significant (p<0.05) difference between control and ASH-WEX treated groups.</p>", "links"=>[], "tags"=>["inhibition", "assessed", "mtt", "assay", "sh-sy5y", "neuro-2a", "cells"], "article_id"=>167909, "categories"=>["Cancer", "Cell Biology"], "users"=>["Hardeep Kataria", "Renu Wadhwa", "Sunil C. Kaul", "Gurcharan Kaur"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055316.g001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Growth_curve_inhibition_as_assessed_by_MTT_assay_in_IMR_32_TGW_SH_SY5Y_and_Neuro_2a_cells_a_/167909", "title"=>"Growth curve inhibition as assessed by MTT assay in IMR-32, TGW, SH-SY5Y and Neuro-2a cells (a).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-31 02:11:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/497808"], "description"=>"<p>IMR-32 cells were treated with 0.5% ASH-WEX and RA for 72 h (a). The evaluation of cell cycle progression was done by DNA staining by propidium iodide. The figure shows representative FACS profiles of the distribution of cells in G0/G1, S, and G2/M phases as analysed by FCS software. (b) Histogram represents percentage distribution of the cells in different phases (G0/G1, S, and G2/M) after ASH-WEX treatment as compared to control. (c) Flow cytometric examination of apoptosis, necrosis and cell viability-the Annexin V/PI assay. Diagrams show four subgroups of cells. Viable (Q1, annexin V-, PI-), early apoptotic (Q2, annexin V+, PI-), late apoptotic (Q3, annexin V+, PI+) and necrotic/damaged (Q4, annexin V-, PI+) are represented in different quadrants. (d) Histogram represents percentage distribution of the cells in different quadrants. “*” represents the statistical significant (p<0.05) difference between control and ASH-WEX treated groups.</p>", "links"=>[], "tags"=>["affects", "events", "imr-32"], "article_id"=>168324, "categories"=>["Cancer", "Cell Biology"], "users"=>["Hardeep Kataria", "Renu Wadhwa", "Sunil C. Kaul", "Gurcharan Kaur"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055316.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ASH_WEX_affects_the_distribution_of_events_in_the_IMR_32_cell_cycle_/168324", "title"=>"ASH-WEX affects the distribution of events in the IMR-32 cell cycle.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-31 02:18:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/498141"], "description"=>"<p>Primer sequences used for semi-quantitative RT-PCR.</p>", "links"=>[], "tags"=>["sequences", "semi-quantitative"], "article_id"=>168665, "categories"=>["Cancer", "Cell Biology"], "users"=>["Hardeep Kataria", "Renu Wadhwa", "Sunil C. Kaul", "Gurcharan Kaur"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055316.t001", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primer_sequences_used_for_semi_quantitative_RT_PCR_/168665", "title"=>"Primer sequences used for semi-quantitative RT-PCR.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-01-31 02:24:25"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[272, 472, 600, 713, 815, 911, 1004, 1094, 1185, 1273, 1358, 1441]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[275, 472, 605, 720, 822, 921, 1013, 1106, 1200, 1289, 1378, 1459, 1531]}]}
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