Bitter Melon Reduces Head and Neck Squamous Cell Carcinoma Growth by Targeting c-Met Signaling
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{"title"=>"Bitter Melon Reduces Head and Neck Squamous Cell Carcinoma Growth by Targeting c-Met Signaling", "type"=>"journal", "authors"=>[{"first_name"=>"Ananthi", "last_name"=>"Rajamoorthi", "scopus_author_id"=>"55887349700"}, {"first_name"=>"Shubham", "last_name"=>"Shrivastava", "scopus_author_id"=>"36718288900"}, {"first_name"=>"Robert", "last_name"=>"Steele", "scopus_author_id"=>"7402223116"}, {"first_name"=>"Pratibha", "last_name"=>"Nerurkar", "scopus_author_id"=>"6602404578"}, {"first_name"=>"Juan G.", "last_name"=>"Gonzalez", "scopus_author_id"=>"57198495976"}, {"first_name"=>"Susan", "last_name"=>"Crawford", "scopus_author_id"=>"7202195248"}, {"first_name"=>"Mark", "last_name"=>"Varvares", "scopus_author_id"=>"7004021479"}, {"first_name"=>"Ratna B.", "last_name"=>"Ray", "scopus_author_id"=>"7402180945"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"370046557", "sgr"=>"84885767020", "doi"=>"10.1371/journal.pone.0078006", "scopus"=>"2-s2.0-84885767020", "pmid"=>"24147107"}, "id"=>"2dd414d8-7d84-39fd-857e-aa4f40dcb5e9", "abstract"=>"Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat, and despite of advances in treatment, the overall survival rate has only modestly improved over the past several years. Thus, there is an urgent need for additional therapeutic modalities. We hypothesized that treatment of HNSCC cells with a dietary product such as bitter melon extract (BME) modulates multiple signaling pathways and regresses HNSCC tumor growth in a preclinical model. We observed a reduced cell proliferation in HNSCC cell lines. The mechanistic studies reveal that treatment of BME in HNSCC cells inhibited c-Met signaling pathway. We also observed that BME treatment in HNSCC reduced phosphoStat3, c-myc and Mcl-1 expression, downstream signaling molecules of c-Met. Furthermore, BME treatment in HNSCC cells modulated the expression of key cell cycle progression molecules leading to halted cell growth. Finally, BME feeding in mice bearing HNSCC xenograft tumor resulted in an inhibition of tumor growth and c-Met expression. Together, our results suggested that BME treatment in HNSCC cells modulates multiple signaling pathways and may have therapeutic potential for treating HNSCC.", "link"=>"http://www.mendeley.com/research/bitter-melon-reduces-head-neck-squamous-cell-carcinoma-growth-targeting-cmet-signaling-1", "reader_count"=>15, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>5, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>5, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>1, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>6, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Austria"=>1, "Turkey"=>1, "United States"=>1, "Switzerland"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1245744"], "description"=>"<p>(A). Gene expression profiling from RNA of mock or BME treated Cal27 cells was performed using SABiosciences cell cycle pathway qRT-PCR arrays. BME treated cells display a pattern of modulated cell proliferation markers (e.g., ATM, CCND1, MCM2 and BIRC5). (B). Cal27 and JHU-22 cells were treated with BME and cell lysates were analyzed for certain cell cycle molecules for verification. The expression of CyclinD1, p21, p27 and survivin was examined by Western blot using specific antibodies. The blots were reprobed with an antibody to GAPDH for comparison of protein load.</p>", "links"=>[], "tags"=>["molecules", "bme", "hnscc"], "article_id"=>826344, "categories"=>["Biological Sciences"], "users"=>["Ananthi Rajamoorthi", "Shubham Shrivastava", "Robert Steele", "Pratibha Nerurkar", "Juan G. Gonzalez", "Susan Crawford", "Mark Varvares", "Ratna B. Ray"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078006.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Modulation_of_cell_cycle_regulatory_molecules_following_BME_treatment_in_HNSCC_cells_/826344", "title"=>"Modulation of cell cycle regulatory molecules following BME treatment in HNSCC cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-17 02:59:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1245747"], "description"=>"<p>(A). Cal27 cells were implanted subcutaneously into the flank of athymic nude mice. Tumor bearing mice were randomized into two groups, and water (control) or BME was gavaged orally for 4 weeks (5 day/wk). Down arrow indicates the BME or water gavage start time. Volume of tumor growth was monitored once a week and presented as a mean. Small bar indicates standard error (*, p<0.05). (B). Representative tumors dissected from the control and BME-fed mice are shown. (C). Western blot of c-Met, c-myc and MCM2 in xenograft tumor tissues isolated from both control and BME fed mice. The blot was reprobed with an antibody to GAPDH for comparison of protein load. (D). The immunohistochemical staining for PCNA in representative tumor section of a control and BME-fed mice (magnification, 40×) are shown. (E). A representative tumor section from control or BME-fed mice stained with hematoxylin and eosin (magnification, 40×) are shown. Arrows indicate the mitosis.</p>", "links"=>[], "tags"=>["bme", "cal27", "xenograft", "nude", "mice"], "article_id"=>826345, "categories"=>["Biological Sciences"], "users"=>["Ananthi Rajamoorthi", "Shubham Shrivastava", "Robert Steele", "Pratibha Nerurkar", "Juan G. Gonzalez", "Susan Crawford", "Mark Varvares", "Ratna B. Ray"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078006.g005", "stats"=>{"downloads"=>8, "page_views"=>229, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Oral_BME_administration_in_Cal27_xenograft_nude_mice_reduces_tumor_growth_/826345", "title"=>"Oral BME administration in Cal27 xenograft nude mice reduces tumor growth.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-17 02:59:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1245741"], "description"=>"<p>(A). HNSCC cells were treated with BME for 24 h, and MTS assay was performed. (B). Cal27 cells were treated with BME for different time points. Cell proliferation was measured in control and BME treated Cal27 cells by Trypan blue exclusion method. The results are presented as means of three different experiments with standard errors. (**, p<0.001).</p>", "links"=>[], "tags"=>["hnscc", "cells", "inhibits"], "article_id"=>826341, "categories"=>["Biological Sciences"], "users"=>["Ananthi Rajamoorthi", "Shubham Shrivastava", "Robert Steele", "Pratibha Nerurkar", "Juan G. Gonzalez", "Susan Crawford", "Mark Varvares", "Ratna B. Ray"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078006.g001", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_BME_treatment_in_HNSCC_cells_inhibits_proliferation_/826341", "title"=>"BME treatment in HNSCC cells inhibits proliferation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-17 02:59:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1245742"], "description"=>"<p>(A). Lysates were prepared from Cal27 cells treated or untreated with BME for 72 h, and subjected to Western blot analysis using a specific antibody to PARP. Following treatment of BME, PARP was cleaved to an 86 kD signature peptide. (B). Treatment of Cal27 cells with BME induced caspase 9 and 3 cleavage. The cleaved product of caspase 9 and caspase 3 are shown. The blot was reprobed with an antibody to GAPDH for comparison of equal protein load. (C). JHU-22 and JHU-29 cells were treated with BME and cell lysates were subjected to Western blot analysis for PARP cleavage using specific antibody. The blot was reprobed with an antibody to GAPDH for comparison of equal protein load.</p>", "links"=>[], "tags"=>["hnscc", "cells", "induced", "parp", "cleavage", "caspase"], "article_id"=>826342, "categories"=>["Biological Sciences"], "users"=>["Ananthi Rajamoorthi", "Shubham Shrivastava", "Robert Steele", "Pratibha Nerurkar", "Juan G. Gonzalez", "Susan Crawford", "Mark Varvares", "Ratna B. Ray"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078006.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_BME_treatment_in_HNSCC_cells_induced_PARP_cleavage_and_caspase_activation_/826342", "title"=>"BME treatment in HNSCC cells induced PARP cleavage and caspase activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-17 02:59:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1245743"], "description"=>"<p>(A). Cal27 cells were treated with BME in a dose dependent manner and reduced c-Met expression was noted by Western blot analysis. The blot was reprobed with an antibody to GAPDH for comparison of equal protein load. (B). The expression levels of phosphoStat3 (Tyr705), c-myc and Mcl-1 in control and BME treated Cal27 cells were examined by Western blot using specific antibodies. The blot was reprobed with an antibody to GAPDH for comparison of protein load. (C). JHU-22 cells were treated with BME for 48 h and cell lysates were analyzed for c-Met and phosphoStat3 expression by Western blot analysis using specific antibody. The blot was reprobed with an antibody to tubulin for comparison of protein load. (D). The expression levels of c-myc and Mcl-1 in control and BME treated JHU-22 cells were examined by Western blot using specific antibodies. The blot was reprobed with an antibody to GAPDH for comparison of protein load.</p>", "links"=>[], "tags"=>["bme", "hnscc", "cells", "decreases", "c-met", "downstream"], "article_id"=>826343, "categories"=>["Biological Sciences"], "users"=>["Ananthi Rajamoorthi", "Shubham Shrivastava", "Robert Steele", "Pratibha Nerurkar", "Juan G. Gonzalez", "Susan Crawford", "Mark Varvares", "Ratna B. Ray"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078006.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Treatment_of_BME_in_HNSCC_cells_decreases_c_Met_protein_expression_and_its_downstream_signaling_pathways_/826343", "title"=>"Treatment of BME in HNSCC cells decreases c-Met protein expression and its downstream signaling pathways.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-17 02:59:56"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}

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"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Medicine and health sciences/Oncology", "average_usage"=>[249, 468, 599, 718, 820, 920, 1008, 1093, 1181, 1281, 1357, 1444, 1517]}]}
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