Proteomic Profiling Reveals That Resveratrol Inhibits HSP27 Expression and Sensitizes Breast Cancer Cells to Doxorubicin Therapy
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{"title"=>"Proteomic Profiling Reveals That Resveratrol Inhibits HSP27 Expression and Sensitizes Breast Cancer Cells to Doxorubicin Therapy", "type"=>"journal", "authors"=>[{"first_name"=>"José", "last_name"=>"Díaz-Chávez", "scopus_author_id"=>"23569516700"}, {"first_name"=>"Miguel A.", "last_name"=>"Fonseca-Sánchez", "scopus_author_id"=>"8615576400"}, {"first_name"=>"Elena", "last_name"=>"Arechaga-Ocampo", "scopus_author_id"=>"23093064600"}, {"first_name"=>"Ali", "last_name"=>"Flores-Pérez", "scopus_author_id"=>"57190024037"}, {"first_name"=>"Yadira", "last_name"=>"Palacios-Rodríguez", "scopus_author_id"=>"56002687400"}, {"first_name"=>"Guadalupe", "last_name"=>"Domínguez-Gómez", "scopus_author_id"=>"55983969700"}, {"first_name"=>"Laurence A.", "last_name"=>"Marchat", "scopus_author_id"=>"6603642720"}, {"first_name"=>"Lizeth", "last_name"=>"Fuentes-Mera", "scopus_author_id"=>"6503976979"}, {"first_name"=>"Guillermo", "last_name"=>"Mendoza-Hernández", "scopus_author_id"=>"55993655800"}, {"first_name"=>"Patricio", "last_name"=>"Gariglio", "scopus_author_id"=>"7005756732"}, {"first_name"=>"César", "last_name"=>"López-Camarillo", "scopus_author_id"=>"8640484800"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"369013302", "sgr"=>"84878322096", "pmid"=>"23724044", "scopus"=>"2-s2.0-84878322096", "isbn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0064378", "issn"=>"19326203"}, "id"=>"edd87e7c-9ff7-3df0-a863-21116d86709d", "abstract"=>"The use of chemopreventive natural compounds represents a promising strategy in the search for novel therapeutic agents in cancer. Resveratrol (3,4',5-trans-trihydroxystilbilene) is a dietary polyphenol found in fruits, vegetables and medicinal plants that exhibits chemopreventive and antitumor effects. In this study, we searched for modulated proteins with preventive or therapeutic potential in MCF-7 breast cancer cells exposed to resveratrol. Using two-dimensional electrophoresis we found significant changes (FC >2.0; p≤0.05) in the expression of 16 proteins in resveratrol-treated MCF-7 cells. Six down-regulated proteins were identified by tandem mass spectrometry (ESI-MS/MS) as heat shock protein 27 (HSP27), translationally-controlled tumor protein, peroxiredoxin-6, stress-induced-phosphoprotein-1, pyridoxine-5'-phosphate oxidase-1 and hypoxanthine-guanine phosphoribosyl transferase; whereas one up-regulated protein was identified as triosephosphate isomerase. Particularly, HSP27 overexpression has been associated to apoptosis inhibition and resistance of human cancer cells to therapy. Consistently, we demonstrated that resveratrol induces apoptosis in MCF-7 cells. Apoptosis was associated with a significant increase in mitochondrial permeability transition, cytochrome c release in cytoplasm, and caspases -3 and -9 independent cell death. Then, we evaluated the chemosensitization effect of increasing concentrations of resveratrol in combination with doxorubicin anti-neoplastic agent in vitro. We found that resveratrol effectively sensitize MCF-7 cells to cytotoxic therapy. Next, we evaluated the relevance of HSP27 targeted inhibition in therapy effectiveness. Results evidenced that HSP27 inhibition using RNA interference enhances the cytotoxicity of doxorubicin. In conclusion, our data indicate that resveratrol may improve the therapeutic effects of doxorubicin in part by cell death induction. We propose that potential modulation of HSP27 levels using natural alternative agents, as resveratrol, may be an effective adjuvant in breast cancer therapy.", "link"=>"http://www.mendeley.com/research/proteomic-profiling-reveals-resveratrol-inhibits-hsp27-expression-sensitizes-breast-cancer-cells-dox", "reader_count"=>40, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>10, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>8, "Other"=>2, "Student > Master"=>11, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>10, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>8, "Other"=>2, "Student > Master"=>11, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>6, "Mathematics"=>1, "Agricultural and Biological Sciences"=>17, "Medicine and Dentistry"=>6, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Chemistry"=>2, "Psychology"=>1, "Computer Science"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>2}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>17}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}}, "reader_count_by_country"=>{"Brazil"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/1068133"], "description"=>"<p>(A) MTT assays of MCF-7 cells treated with either doxorobucin (5 µM) or resveratrol (100 and 250 µM) alone, or with combinations of increased concentrations of resveratrol (50, 100, 150. 200 and 250 µM) and doxorubicin (5 µM). (B) Western blot analysis of HSP27 and β-actin expression after resveratrol (100, 150, 200 and 250 µM) treatment of MCF-7 cells. (C) Western blot analysis of HSP27 and β-actin proteins in MCF-7 cells transfected with three short-harping interfering RNA constructions (pSilencer-HSP27.1, -HSP27.2 and -HSP27.3). (D) Densitometric analysis of bands shown in panel C. Pixels corresponding to β-actin expression in control (non-transfected) cells were taken as 100% and used to normalize HSP27 data. (E) Cell viability percentage of HSP27-deficient MCF-7 cells treated with doxorubicin (5 µM) for 48 h. Cell viability was determined by MTT assay. Assays were performed by triplicate and data was expressed as means ±SD. Asterisks indicate p<0.05 compared to controls.</p>", "links"=>[], "tags"=>["Molecular cell biology", "gene expression", "RNA interference", "oncology", "Cancer risk factors", "chemoprevention", "Cancer treatment", "Chemotherapy and drug treatment", "Cancers and neoplasms", "Breast tumors", "Basic cancer research", "Cancer prevention", "Oncology agents", "hsp27", "sensitizes", "mcf-7", "cells", "doxorubicin"], "article_id"=>707214, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jose Diaz-Chavez", "Miguel A. Fonseca-Sánchez", "Elena Arechaga-Ocampo", "Ali Flores-Pérez", "Yadira Palacios-Rodríguez", "Guadalupe Domínguez-Gómez", "Laurence A. Marchat", "Lizeth Fuentes-Mera", "Guillermo Mendoza-Hernández", "Patricio Gariglio", "César López-Camarillo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0064378.g004", "stats"=>{"downloads"=>2, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Resveratrol_and_HSP27_silencing_sensitizes_MCF_7_cells_to_doxorubicin_treatment_/707214", "title"=>"Resveratrol and HSP27 silencing sensitizes MCF-7 cells to doxorubicin treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-27 02:00:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1068129"], "description"=>"<p>(A) Representative 2DE gels of MCF-7 cells treated with 250 µM resveratrol (bottom image) or non-treated control (upper image). Protein spots selected for identification by spectrometry (ESI-MS/MS) are marked with white arrows. (B) Enlarged sections of representative 2DE gels showing differential expression of spots between resveratrol treated and non-treated cells. Right, graphs showing individual and averaged relative intensities of the selected spots. NT, non-treated cells; Rsv, resveratrol treated cells.</p>", "links"=>[], "tags"=>["Molecular cell biology", "gene expression", "RNA interference", "oncology", "Cancer risk factors", "chemoprevention", "Cancer treatment", "Chemotherapy and drug treatment", "Cancers and neoplasms", "Breast tumors", "Basic cancer research", "Cancer prevention", "Oncology agents", "profiles", "mcf-7", "cancer", "cells", "treated"], "article_id"=>707211, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jose Diaz-Chavez", "Miguel A. Fonseca-Sánchez", "Elena Arechaga-Ocampo", "Ali Flores-Pérez", "Yadira Palacios-Rodríguez", "Guadalupe Domínguez-Gómez", "Laurence A. Marchat", "Lizeth Fuentes-Mera", "Guillermo Mendoza-Hernández", "Patricio Gariglio", "César López-Camarillo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0064378.g001", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Proteomic_profiles_of_MCF_7_breast_cancer_cells_treated_with_resveratrol_/707211", "title"=>"Proteomic profiles of MCF-7 breast cancer cells treated with resveratrol.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-27 02:00:11"}

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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/Biochemistry", "average_usage"=>[266, 468, 593, 703, 804, 903, 993, 1084, 1171, 1256, 1339, 1422, 1492]}, {"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/Genetics", "average_usage"=>[284, 491, 620, 738, 843, 945, 1043, 1137, 1225, 1315, 1400, 1479, 1555]}, {"subject_area"=>"/Medicine and health sciences/Oncology", "average_usage"=>[249, 468, 599, 718, 820, 920, 1008, 1093, 1181, 1281, 1357, 1444, 1517]}, {"subject_area"=>"/Medicine and health sciences/Pharmaceutics", "average_usage"=>[254, 457, 591, 700, 808, 906, 1001, 1093, 1185, 1276, 1373, 1457, 1535]}, {"subject_area"=>"/Medicine and health sciences/Pharmacology", "average_usage"=>[265, 471, 604, 723, 827, 926, 1022, 1113, 1210, 1290, 1377, 1454, 1532]}]}
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