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{"title"=>"Melittin Suppresses HIF-1α/VEGF Expression through Inhibition of ERK and mTOR/p70S6K Pathway in Human Cervical Carcinoma Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Jae Moon", "last_name"=>"Shin", "scopus_author_id"=>"55272416500"}, {"first_name"=>"Yun Jeong", "last_name"=>"Jeong", "scopus_author_id"=>"15044646400"}, {"first_name"=>"Hyun Ji", "last_name"=>"Cho", "scopus_author_id"=>"57013873500"}, {"first_name"=>"Kwan Kyu", "last_name"=>"Park", "scopus_author_id"=>"56984258600"}, {"first_name"=>"Il Kyung", "last_name"=>"Chung", "scopus_author_id"=>"7201868006"}, {"first_name"=>"In Kyu", "last_name"=>"Lee", "scopus_author_id"=>"36071537600"}, {"first_name"=>"Jong Young", "last_name"=>"Kwak", "scopus_author_id"=>"7202648921"}, {"first_name"=>"Hyeun Wook", "last_name"=>"Chang", "scopus_author_id"=>"16026254400"}, {"first_name"=>"Cheorl Ho", "last_name"=>"Kim", "scopus_author_id"=>"7409877266"}, {"first_name"=>"Sung Kwon", "last_name"=>"Moon", "scopus_author_id"=>"7401616572"}, {"first_name"=>"Wun Jae", "last_name"=>"Kim", "scopus_author_id"=>"8081691400"}, {"first_name"=>"Yung Hyun", "last_name"=>"Choi", "scopus_author_id"=>"13407149200"}, {"first_name"=>"Young Chae", "last_name"=>"Chang", "scopus_author_id"=>"7501843107"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"369424051", "doi"=>"10.1371/journal.pone.0069380", "sgr"=>"84880757335", "scopus"=>"2-s2.0-84880757335", "pmid"=>"23936001"}, "id"=>"510f393b-a1aa-3233-b42f-9a34c794d373", "abstract"=>"OBJECTIVE: Melittin (MEL), a major component of bee venom, has been associated with various diseases including arthritis, rheumatism and various cancers. In this study, the anti-angiogenic effects of MEL in CaSki cells that were responsive to the epidermal growth factor (EGF) were examined.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: MEL decreased the EGF-induced hypoxia-inducible factor-1α (HIF-1α) protein and significantly regulated angiogenesis and tumor progression. We found that inhibition of the HIF-1α protein level is due to the shortened half-life by MEL. Mechanistically, MEL specifically inhibited the EGF-induced HIF-1α expression by suppressing the phosphorylation of ERK, mTOR and p70S6K. It also blocked the EGF-induced DNA binding activity of HIF-1α and the secretion of the vascular endothelial growth factor (VEGF). Furthermore, the chromatin immunoprecipitation (ChIP) assay revealed that MEL reduced the binding of HIF-1α to the VEGF promoter HRE region. The anti-angiogenesis effects of MEL were confirmed through a matrigel plus assay.\\n\\nCONCLUSIONS: MEL specifically suppressed EGF-induced VEGF secretion and new blood vessel formation by inhibiting HIF-1α. These results suggest that MEL may inhibit human cervical cancer progression and angiogenesis by inhibiting HIF-1α and VEGF expression.", "link"=>"http://www.mendeley.com/research/melittin-suppresses-hif1%CE%B1vegf-expression-through-inhibition-erk-mtorp70s6k-pathway-human-cervical-ca", "reader_count"=>16, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Student > Master"=>4, "Student > Bachelor"=>2, "Student > Doctoral Student"=>1, "Researcher"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Student > Master"=>4, "Student > Bachelor"=>2, "Student > Doctoral Student"=>1, "Researcher"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>7, "Neuroscience"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Sweden"=>1, "Argentina"=>1}, "group_count"=>0}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/1127390"], "description"=>"<p>(A) Dose-dependent effect of MEL on the viability of CaSki cells. Cells were treated with the indicated concentrations of MEL for 24 h. Viability was determined by WST-1 assay. Values represent the means ± SD of triplicate assays. *, <i>p</i><0.05 as compared to untreated control. Results were analyzed using one-way ANOVA. (B) Cells were pretreated with the indicated concentrations of MEL for 30 min, and then induced by EGF treatment for 6 h. (C) Cells were pretreated with the indicated concentrations of MEL for 30 min, and then induced by CoCl₂ treatment for 6 h. Nuclear extracts were subjected to Western blot using antibodies against HIF-1α and HIF-1β.</p>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "biotechnology", "Molecular cell biology", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Cancer treatment", "Antiangiogenesis therapy", "Cancers and neoplasms", "Gynecological tumors", "Cervical cancer", "Basic cancer research", "inhibited", "accumulation", "induced", "egf", "caski"], "article_id"=>752267, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jae-Moon Shin", "Yun-Jeong Jeong", "Hyun-Ji Cho", "Kwan-Kyu Park", "Il-Kyung Chung", "In-Kyu Lee", "Jong-Young Kwak", "Hyeun-Wook Chang", "Cheorl-Ho Kim", "Sung-Kwon Moon", "Wun-Jae Kim", "Yung-Hyun Choi", "Young-Chae Chang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069380.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Melittin_MEL_inhibited_the_HIF_1_945_protein_accumulation_induced_by_the_EGF_in_the_CaSki_cells_/752267", "title"=>"Melittin (MEL) inhibited the HIF-1α protein accumulation induced by the EGF in the CaSki cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-23 03:16:11"}
• {"files"=>["https://ndownloader.figshare.com/files/1127391"], "description"=>"<p>(A) RT-PCR analysis of HIF-1α mRNA was carried out using total RNA prepared from CaSki cells incubated with EGF treatment for 12 h in the presence or absence of the indicated concentrations of MEL. (B) Cells were pretreated with the indicated EGF for 6 h, and then were treated to CHX time-dependent. (C) Cells were pretreated with the indicated EGF for 6 h. After 6 h, it was cotreated to MEL and CHX (10 µM) time-dependent. (D) Levels of HIF-1α protein were determined by measuring the density of HIF-1α protein band.</p>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "biotechnology", "Molecular cell biology", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Cancer treatment", "Antiangiogenesis therapy", "Cancers and neoplasms", "Gynecological tumors", "Cervical cancer", "Basic cancer research", "inhibited", "decreasing"], "article_id"=>752268, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jae-Moon Shin", "Yun-Jeong Jeong", "Hyun-Ji Cho", "Kwan-Kyu Park", "Il-Kyung Chung", "In-Kyu Lee", "Jong-Young Kwak", "Hyeun-Wook Chang", "Cheorl-Ho Kim", "Sung-Kwon Moon", "Wun-Jae Kim", "Yung-Hyun Choi", "Young-Chae Chang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069380.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Melittin_MEL_inhibited_the_HIF_1_945_expression_by_decreasing_its_stability_/752268", "title"=>"Melittin (MEL) inhibited the HIF-1α expression by decreasing its stability.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-23 03:16:11"}
• {"files"=>["https://ndownloader.figshare.com/files/1127392"], "description"=>"<p>(A) Effect of MEL on EGF-induced signaling leading to the expression of HIF-1α in CaSki cells. CaSki cells were pretreated with the indicated concentrations of MEL for 1 h, followed by incubation with EGF for 30 min. The phosphorylated levels of EGFR, P38, ERK, JNK, Akt, mTOR and p70S6K were determined by Western blot analysis. (B) Effects of MEL and inhibitors on EGF-induced expression of HIF-1α in CaSki cells. CaSki cells were pretreated with MEL, SB203580, SP600125, PD98059, wortmannin, rapamycin for 30 min, and then induced by EGF treatment for 6 h. Nuclear extracts were subjected to Western blot using antibodies against HIF-1α or β-actin. Data represents the means ± SD of three independent experiments. *, <i>p</i><0.05 as compared to EGF-treated control. Results were analyzed using one-way ANOVA.</p>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "biotechnology", "Molecular cell biology", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Cancer treatment", "Antiangiogenesis therapy", "Cancers and neoplasms", "Gynecological tumors", "Cervical cancer", "Basic cancer research", "suppressed", "egf-induced", "synthesis", "inhibiting", "erk", "pathways", "caski"], "article_id"=>752269, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jae-Moon Shin", "Yun-Jeong Jeong", "Hyun-Ji Cho", "Kwan-Kyu Park", "Il-Kyung Chung", "In-Kyu Lee", "Jong-Young Kwak", "Hyeun-Wook Chang", "Cheorl-Ho Kim", "Sung-Kwon Moon", "Wun-Jae Kim", "Yung-Hyun Choi", "Young-Chae Chang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069380.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Melittin_MEL_suppressed_the_EGF_induced_HIF_1_945_protein_synthesis_by_inhibiting_the_ERK_and_mTOR_p70S6K_signaling_pathways_in_the_CaSki_cells_/752269", "title"=>"Melittin (MEL) suppressed the EGF-induced HIF-1α protein synthesis by inhibiting the ERK and mTOR/p70S6K signaling pathways in the CaSki cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-23 03:16:11"}
• {"files"=>["https://ndownloader.figshare.com/files/1127393"], "description"=>"<p>(A) RT-PCR analysis of VEGF, and GLUT-1 mRNA was carried out using total RNA prepared from CaSki cells incubated with EGF treatment for 12 h in the presence or absence of the indicated concentrations of MEL. (B) CaSki cells were transiently co-transfected with a reporter gene, pGL3-HRE-Luciferase, and pRL-CMV as a reference. Following incubation for 24 h, the cells were incubated with EGF treatment in the presence or absence of indicated concentration of MEL. (C) VEGF protein expression was evaluated by ELISA in culture supernatant of CaSki cells after incubation under EGF treatment in the presence or absence of the indicated concentrations of MEL. (D) CaSki cells were treated with MEL on EGF-induced for 6 h. The immunoprecipitated DNA with mouse normal IgG and HIF-1α antibody was amplified by PCR analysis for VEF promoter HRE region.</p>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "biotechnology", "Molecular cell biology", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Cancer treatment", "Antiangiogenesis therapy", "Cancers and neoplasms", "Gynecological tumors", "Cervical cancer", "Basic cancer research", "abolished", "egf-induced", "vegf", "caski"], "article_id"=>752270, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jae-Moon Shin", "Yun-Jeong Jeong", "Hyun-Ji Cho", "Kwan-Kyu Park", "Il-Kyung Chung", "In-Kyu Lee", "Jong-Young Kwak", "Hyeun-Wook Chang", "Cheorl-Ho Kim", "Sung-Kwon Moon", "Wun-Jae Kim", "Yung-Hyun Choi", "Young-Chae Chang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069380.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Melittin_MEL_abolished_the_expression_secretion_of_the_EGF_induced_VEGF_in_the_CaSKi_cells_/752270", "title"=>"Melittin (MEL) abolished the expression/secretion of the EGF-induced VEGF in the CaSKi cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-23 03:16:11"}
• {"files"=>["https://ndownloader.figshare.com/files/1127394"], "description"=>"<p>(A and B) CaSki 3×10⁴ cells/ml were mixed with 0.5 ml of Matrigel in the presence or absence of EGF (500 ng/ml) and MEL (1 and 2 µg/ml) in vivo. (C and D) Matrigel migration assay was carried out MEL (1 and 2 µg/ml) in the presence of EGF (20 ng/ml). After 24 h incubation, cells bottom side of filter were fixed, stained and counted. Data represents the means ± SD of three independent experiments. *, <i>p</i><0.05 as compared to EGF-treated control. Results were analyzed using one-way ANOVA.</p>", "links"=>[], "tags"=>["Biochemistry", "drug discovery", "biotechnology", "Molecular cell biology", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Cancer treatment", "Antiangiogenesis therapy", "Cancers and neoplasms", "Gynecological tumors", "Cervical cancer", "Basic cancer research", "suppressed", "egf-induced", "angiogenesis", "caski"], "article_id"=>752271, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jae-Moon Shin", "Yun-Jeong Jeong", "Hyun-Ji Cho", "Kwan-Kyu Park", "Il-Kyung Chung", "In-Kyu Lee", "Jong-Young Kwak", "Hyeun-Wook Chang", "Cheorl-Ho Kim", "Sung-Kwon Moon", "Wun-Jae Kim", "Yung-Hyun Choi", "Young-Chae Chang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069380.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Melittin_MEL_suppressed_the_EGF_induced_migration_and_angiogenesis_in_the_CaSki_cells_/752271", "title"=>"Melittin (MEL) suppressed the EGF-induced migration and angiogenesis in the CaSki cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-23 03:16:11"}

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• {"unique-ip"=>"14", "full-text"=>"19", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
• {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
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• {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
• {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
• {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
• {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

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F1000Prime