Nanomicellar Formulation of Clotrimazole Improves Its Antitumor Action toward Human Breast Cancer Cells
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{"title"=>"Nanomicellar formulation of clotrimazole improves its antitumor action toward human breast cancer cells", "type"=>"journal", "authors"=>[{"first_name"=>"Mariah C.", "last_name"=>"Marcondes", "scopus_author_id"=>"16175648600"}, {"first_name"=>"Anne C.S.", "last_name"=>"Fernandes", "scopus_author_id"=>"57199406807"}, {"first_name"=>"Ivaldo", "last_name"=>"Itabaiana", "scopus_author_id"=>"55482773400"}, {"first_name"=>"Rodrigo O.M.A.", "last_name"=>"De Souza", "scopus_author_id"=>"7102470737"}, {"first_name"=>"Mauro", "last_name"=>"Sola-Penna", "scopus_author_id"=>"6604018187"}, {"first_name"=>"Patricia", "last_name"=>"Zancan", "scopus_author_id"=>"9042312400"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84939202541", "pui"=>"605585784", "doi"=>"10.1371/journal.pone.0130555", "sgr"=>"84939202541", "pmid"=>"26098874"}, "id"=>"8f508423-a5aa-3d2d-93e7-9cff784d7e75", "abstract"=>"BACKGROUND: Although demonstrated as a selective anticancer drug, the clinical use of clotrimazole (CTZ) is limited due to its low solubility in hydrophilic fluids. Thus, we prepared a water-soluble nanomicellar formulation of CTZ (nCTZ) and tested on the human breast cancer cell line MCF-7 biology. METHODOLOGY/PRINCIPAL FINDINGS: CTZ was nanoencapsulated in tween 80 micelles, which generated nanomicelles of, approximately, 17 nm of diameter. MCF-7 cells were treated with nCTZ and unencapsulated DMSO-solubilized drug (sCTZ) was used for comparison. After treatment, the cells were evaluated in terms of metabolism, proliferation, survival and structure. We found that nCTZ was more efficient than sCTZ at inhibiting glycolytic and other cytosolic and mitochondrial enzymes. Moreover, this increased activity was also observed for lactate production, intracellular ATP content, ROS production and antioxidant potential. As a consequence, nCTZ-treated MCF-7 cells displayed alterations to the plasma membrane, mitochondria and the nucleus. Finally, nCTZ induced both apoptosis and necrosis in MCF-7 cells. CONCLUSIONS/SIGNIFICANCE: MCF-7 cells are more sensible to nCTZ than to sCTZ. This was especially evident on regard to antioxidant potential, which is an important cell defense against drugs that affect cell metabolism. Moreover, this water-soluble formulation of CTZ strengths its potential use as an anticancer medicine.", "link"=>"http://www.mendeley.com/research/nanomicellar-formulation-clotrimazole-improves-antitumor-action-toward-human-breast-cancer-cells", "reader_count"=>8, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>1, "Chemistry"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"India"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2130076"], "description"=>"<p>The experimental procedures are described in Materials and Methods. Panel A: non-treated control cells (inset: MCF-7 cells treated with nanomicelles prepared in the absence of CTZ). Panel B: MCF-7 cells treated with 50 μM <sub>n</sub>CTZ. Panel C: MCF-7 cells treated with 100 μM <sub>n</sub>CTZ. Bar = 50 μm. Images are representative of a series of at least four experiments.</p>", "links"=>[], "tags"=>["ROS production", "CTZ strengths", "Nanomicellar Formulation", "cell defense", "lactate production", "anticancer medicine", "Cell metabolism", "plasma membrane", "nCTZ", "17 nm", "intracellular ATP content", "Antitumor Action", "anticancer drug", "tween 80 micelles", "Human Breast Cancer Cells BackgroundAlthough", "sCTZ", "mitochondrial enzymes", "mcf"], "article_id"=>1457612, "categories"=>["Uncategorised"], "users"=>["Mariah C. Marcondes", "Anne C. S. Fernandes", "Ivaldo Itabaiana Jr.", "Rodrigo O. M. A. de Souza", "Mauro Sola-Penna", "Patricia Zancan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130555.g006", "stats"=>{"downloads"=>1, "page_views"=>48, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Scanning_electron_microscopy_of_MCF_7_cells_treated_with_nanomicellar_CTZ_/1457612", "title"=>"Scanning electron microscopy of MCF-7 cells treated with nanomicellar CTZ.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-22 04:25:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2130071"], "description"=>"<p>ROS production (panel A), G6PDH activity (panel B), total glutathione content (panel C), GSSG content (panel D), GSH content (panel E) and GSSG/GSH ratio (panel F) were assessed as described in Materials and Methods in the absence and in the presence of 50 or 100 μM of DMSO-solubilized or a nanomicellar preparation of CTZ. In the absence of CTZ the appropriate amount of DMSO (1% vol/vol) or CTZ-free nanomicellar preparation was added as controls. The results for these controls were not different from the control with no addition. Values are the means ± standard error of the mean, for at least 4 independent experiments (n = 4). * P < 0.05 compared to control and # P < 0.05 compared to DMSO-solubilized CTZ (two-tailed ANOVA, Bonferroni’s port-hoc test).</p>", "links"=>[], "tags"=>["ROS production", "CTZ strengths", "Nanomicellar Formulation", "cell defense", "lactate production", "anticancer medicine", "Cell metabolism", "plasma membrane", "nCTZ", "17 nm", "intracellular ATP content", "Antitumor Action", "anticancer drug", "tween 80 micelles", "Human Breast Cancer Cells BackgroundAlthough", "sCTZ", "mitochondrial enzymes", "mcf"], "article_id"=>1457607, "categories"=>["Uncategorised"], "users"=>["Mariah C. Marcondes", "Anne C. S. Fernandes", "Ivaldo Itabaiana Jr.", "Rodrigo O. M. A. de Souza", "Mauro Sola-Penna", "Patricia Zancan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130555.g004", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_nanomicellar_CTZ_on_ROS_production_and_oxidative_stress_protection_of_MCF_7_cells_/1457607", "title"=>"Effects of nanomicellar CTZ on ROS production and oxidative stress protection of MCF-7 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-22 04:25:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2130070"], "description"=>"<p>SDH activity (panel A), mitochondrial transmembrane potential (panel B) and intracellular ATP content (panel C) were assessed as described in Materials and Methods in the absence and in the presence of 50 or 100 μM of DMSO-solubilized or a nanomicellar preparation of CTZ. In the absence of CTZ the appropriate amount of DMSO (1% vol/vol) or CTZ-free nanomicellar preparation was added as controls. The results for these controls were not different from the control with no addition. Malonate (12 mM) was used as a control for SDH inhibition. Values are the means ± standard error of the mean, for at least 4 independent experiments (n = 4). * P < 0.05 compared to control and # P < 0.05 compared to DMSO-solubilized CTZ (two-tailed ANOVA, Bonferroni’s port-hoc test).</p>", "links"=>[], "tags"=>["ROS production", "CTZ strengths", "Nanomicellar Formulation", "cell defense", "lactate production", "anticancer medicine", "Cell metabolism", "plasma membrane", "nCTZ", "17 nm", "intracellular ATP content", "Antitumor Action", "anticancer drug", "tween 80 micelles", "Human Breast Cancer Cells BackgroundAlthough", "sCTZ", "mitochondrial enzymes", "mcf"], "article_id"=>1457606, "categories"=>["Uncategorised"], "users"=>["Mariah C. Marcondes", "Anne C. S. Fernandes", "Ivaldo Itabaiana Jr.", "Rodrigo O. M. A. de Souza", "Mauro Sola-Penna", "Patricia Zancan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130555.g003", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_nanomicellar_CTZ_on_mitochondrial_parameters_and_on_intracellular_ATP_levels_/1457606", "title"=>"Effects of nanomicellar CTZ on mitochondrial parameters and on intracellular ATP levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-22 04:25:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2130081"], "description"=>"<p>The experimental procedures are described in Materials and Methods. Panel A: non-treated control cells. Panel B: MCF-7 cells treated with 50 μM <sub>n</sub>CTZ. Panel C: MCF-7 cells treated with 100 μM <sub>n</sub>CTZ. Panel D: MCF-7 cells treated with nanomicelles prepared in the absence of CTZ. Bar = 5 μm. Images are representative of a series of at least four experiments.</p>", "links"=>[], "tags"=>["ROS production", "CTZ strengths", "Nanomicellar Formulation", "cell defense", "lactate production", "anticancer medicine", "Cell metabolism", "plasma membrane", "nCTZ", "17 nm", "intracellular ATP content", "Antitumor Action", "anticancer drug", "tween 80 micelles", "Human Breast Cancer Cells BackgroundAlthough", "sCTZ", "mitochondrial enzymes", "mcf"], "article_id"=>1457615, "categories"=>["Uncategorised"], "users"=>["Mariah C. Marcondes", "Anne C. S. Fernandes", "Ivaldo Itabaiana Jr.", "Rodrigo O. M. A. de Souza", "Mauro Sola-Penna", "Patricia Zancan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130555.g008", "stats"=>{"downloads"=>0, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transmission_electron_microscopy_of_the_nuclei_of_MCF_7_cells_treated_with_nanomicellar_CTZ_/1457615", "title"=>"Transmission electron microscopy of the nuclei of MCF-7 cells treated with nanomicellar CTZ.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-22 04:25:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2130082"], "description"=>"<p>The experimental procedures are described in Materials and Methods. Panel A: non-treated control cells. Panel B: MCF-7 cells treated with 50 μM <sub>n</sub>CTZ. Panel C: MCF-7 cells treated with 100 μM <sub>n</sub>CTZ. The percentage of cells in each quadrant is given.</p>", "links"=>[], "tags"=>["ROS production", "CTZ strengths", "Nanomicellar Formulation", "cell defense", "lactate production", "anticancer medicine", "Cell metabolism", "plasma membrane", "nCTZ", "17 nm", "intracellular ATP content", "Antitumor Action", "anticancer drug", "tween 80 micelles", "Human Breast Cancer Cells BackgroundAlthough", "sCTZ", "mitochondrial enzymes", "mcf"], "article_id"=>1457616, "categories"=>["Uncategorised"], "users"=>["Mariah C. Marcondes", "Anne C. S. Fernandes", "Ivaldo Itabaiana Jr.", "Rodrigo O. M. A. de Souza", "Mauro Sola-Penna", "Patricia Zancan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130555.g009", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FACS_analyses_of_MCF_7_cells_treated_with_nanomicellar_CTZ_/1457616", "title"=>"FACS analyses of MCF-7 cells treated with nanomicellar CTZ.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-22 04:25:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2130080"], "description"=>"<p>The experimental procedures are described in Materials and Methods. Panel A: non-treated control cells. Panel B: MCF-7 cells treated with 50 μM <sub>n</sub>CTZ. Panel C: MCF-7 cells treated with 100 μM <sub>n</sub>CTZ. Panel D: MCF-7 cells treated with nanomicelles prepared in the absence of CTZ. Bar = 5 μm. Images are representative of a series of at least four experiments.</p>", "links"=>[], "tags"=>["ROS production", "CTZ strengths", "Nanomicellar Formulation", "cell defense", "lactate production", "anticancer medicine", "Cell metabolism", "plasma membrane", "nCTZ", "17 nm", "intracellular ATP content", "Antitumor Action", "anticancer drug", "tween 80 micelles", "Human Breast Cancer Cells BackgroundAlthough", "sCTZ", "mitochondrial enzymes", "mcf"], "article_id"=>1457614, "categories"=>["Uncategorised"], "users"=>["Mariah C. Marcondes", "Anne C. S. Fernandes", "Ivaldo Itabaiana Jr.", "Rodrigo O. M. A. de Souza", "Mauro Sola-Penna", "Patricia Zancan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130555.g007", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transmission_electron_microscopy_of_mitochondria_of_MCF_7_cells_treated_with_nanomicellar_CTZ_/1457614", "title"=>"Transmission electron microscopy of mitochondria of MCF-7 cells treated with nanomicellar CTZ.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-22 04:25:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2130075"], "description"=>"<p>The experimental procedures are described in Materials and Methods. Panel A: non-treated control cells (inset: MCF-7 cells treated with nanomicelles prepared in the absence of CTZ). Panel B: MCF-7 cells treated with 50 μM <sub>n</sub>CTZ. Panel C: MCF-7 cells treated with 100 μM <sub>n</sub>CTZ. Bar = 50 μm. Images are representative of a series of at least four experiments.</p>", "links"=>[], "tags"=>["ROS production", "CTZ strengths", "Nanomicellar Formulation", "cell defense", "lactate production", "anticancer medicine", "Cell metabolism", "plasma membrane", "nCTZ", "17 nm", "intracellular ATP content", "Antitumor Action", "anticancer drug", "tween 80 micelles", "Human Breast Cancer Cells BackgroundAlthough", "sCTZ", "mitochondrial enzymes", "mcf"], "article_id"=>1457611, "categories"=>["Uncategorised"], "users"=>["Mariah C. Marcondes", "Anne C. S. Fernandes", "Ivaldo Itabaiana Jr.", "Rodrigo O. M. A. de Souza", "Mauro Sola-Penna", "Patricia Zancan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130555.g005", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Giemsa_optical_microscopy_of_MCF_7_cells_treated_with_nanomicellar_CTZ_/1457611", "title"=>"Giemsa optical microscopy of MCF-7 cells treated with nanomicellar CTZ.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-22 04:25:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2130069"], "description"=>"<p>The activities of the glycolytic enzymes HK (panel A), PFK (panel B) and PK (panel C) and lactate production (panel D) were assessed as described in Materials and Methods in the absence and in the presence of 50 or 100 μM of DMSO-solubilized or a nanomicellar preparation of CTZ. In the absence of CTZ the appropriate amount of DMSO (1% vol/vol) or CTZ-free nanomicellar preparation was added as controls. The results for these controls were not different from the control with no addition. Values are the means ± standard error of the mean, for at least 4 independent experiments (n = 4). * P < 0.05 compared to control and # P < 0.05 compared to DMSO-solubilized CTZ (two-tailed ANOVA, Bonferroni’s port-hoc test).</p>", "links"=>[], "tags"=>["ROS production", "CTZ strengths", "Nanomicellar Formulation", "cell defense", "lactate production", "anticancer medicine", "Cell metabolism", "plasma membrane", "nCTZ", "17 nm", "intracellular ATP content", "Antitumor Action", "anticancer drug", "tween 80 micelles", "Human Breast Cancer Cells BackgroundAlthough", "sCTZ", "mitochondrial enzymes", "mcf"], "article_id"=>1457605, "categories"=>["Uncategorised"], "users"=>["Mariah C. Marcondes", "Anne C. S. Fernandes", "Ivaldo Itabaiana Jr.", "Rodrigo O. M. A. de Souza", "Mauro Sola-Penna", "Patricia Zancan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130555.g002", "stats"=>{"downloads"=>2, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_nanomicellar_CTZ_on_glycolytic_parameters_/1457605", "title"=>"Effects of nanomicellar CTZ on glycolytic parameters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-22 04:25:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2130068"], "description"=>"<p>Nanomicelles were prepared as described in Materials and Methods in the presence or absence of CTZ. The size of the nanomicelles was analyzed by dynamic light scattering as described above. Panel A: nanomicelles prepared in the absence of CTZ. Panel B: CTZ-containing nanomicelles. Panel C: MCF-7 cell viability evaluated by the MTT assay in the presence of soluble CTZ (black circles) or a nanomicellar preparation of the drug (white circles). Panel D: MCF-7 cell viability evaluated by LDH activity that leaked from the cells in the presence of soluble CTZ (black circles) or a nanomicellar preparation of the drug (white circles). Plotted points are the means ± standard error of the mean, for at least 4 independent experiments (n = 4).</p>", "links"=>[], "tags"=>["ROS production", "CTZ strengths", "Nanomicellar Formulation", "cell defense", "lactate production", "anticancer medicine", "Cell metabolism", "plasma membrane", "nCTZ", "17 nm", "intracellular ATP content", "Antitumor Action", "anticancer drug", "tween 80 micelles", "Human Breast Cancer Cells BackgroundAlthough", "sCTZ", "mitochondrial enzymes", "mcf"], "article_id"=>1457604, "categories"=>["Uncategorised"], "users"=>["Mariah C. Marcondes", "Anne C. S. Fernandes", "Ivaldo Itabaiana Jr.", "Rodrigo O. M. A. de Souza", "Mauro Sola-Penna", "Patricia Zancan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130555.g001", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Size_characterization_and_initial_effects_of_CTZ_containing_nanomicelles_/1457604", "title"=>"Size characterization and initial effects of CTZ-containing nanomicelles.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-22 04:25:46"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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