دورية أكاديمية
Cytotoxic effect of a novel naphthylchalcone against multiple cancer cells focusing on hematologic malignancies.
العنوان: | Cytotoxic effect of a novel naphthylchalcone against multiple cancer cells focusing on hematologic malignancies. |
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المؤلفون: | Maioral MF; Laboratório de Oncologia Experimental e Hemopatias, Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, Campus Trindade, CEP: 88040-900, Florianópolis, SC, Brazil; Programa de Pós-Graduação em Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil., Bodack CDN; Laboratório de Oncologia Experimental e Hemopatias, Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, Campus Trindade, CEP: 88040-900, Florianópolis, SC, Brazil., Stefanes NM; Laboratório de Oncologia Experimental e Hemopatias, Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, Campus Trindade, CEP: 88040-900, Florianópolis, SC, Brazil; Programa de Pós-Graduação em Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil., Bigolin Á; Laboratório de Oncologia Experimental e Hemopatias, Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, Campus Trindade, CEP: 88040-900, Florianópolis, SC, Brazil; Programa de Pós-Graduação em Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil., Mascarello A; Laboratório Estrutura e Atividade, Departamento de Química, Universidade Federal de Santa Catarina, Campus Trindade, CEP: 88040-900, Florianópolis, SC, Brazil., Chiaradia-Delatorre LD; Laboratório Estrutura e Atividade, Departamento de Química, Universidade Federal de Santa Catarina, Campus Trindade, CEP: 88040-900, Florianópolis, SC, Brazil., Yunes RA; Laboratório Estrutura e Atividade, Departamento de Química, Universidade Federal de Santa Catarina, Campus Trindade, CEP: 88040-900, Florianópolis, SC, Brazil., Nunes RJ; Laboratório Estrutura e Atividade, Departamento de Química, Universidade Federal de Santa Catarina, Campus Trindade, CEP: 88040-900, Florianópolis, SC, Brazil., Santos-Silva MC; Laboratório de Oncologia Experimental e Hemopatias, Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, Campus Trindade, CEP: 88040-900, Florianópolis, SC, Brazil; Programa de Pós-Graduação em Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil. Electronic address: maria.claudia.silva@ufsc.br. |
المصدر: | Biochimie [Biochimie] 2017 Sep; Vol. 140, pp. 48-57. Date of Electronic Publication: 2017 Jun 10. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 1264604 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1638-6183 (Electronic) Linking ISSN: 03009084 NLM ISO Abbreviation: Biochimie Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Paris : Editions Scientifiques Elsevier Original Publication: Paris. |
مواضيع طبية MeSH: | Chalcones*/chemical synthesis , Chalcones*/chemistry , Chalcones*/pharmacology , Cytotoxins*/chemical synthesis , Cytotoxins*/chemistry , Cytotoxins*/pharmacology, Apoptosis/*drug effects , Gene Expression Regulation, Neoplastic/*drug effects , Hematologic Neoplasms/*drug therapy , Neoplasm Proteins/*biosynthesis, A549 Cells ; Animals ; Drug Screening Assays, Antitumor ; Female ; HL-60 Cells ; HeLa Cells ; Hematologic Neoplasms/genetics ; Hematologic Neoplasms/metabolism ; Hematologic Neoplasms/pathology ; Humans ; Jurkat Cells ; Male ; Mice ; NIH 3T3 Cells ; Neoplasm Proteins/genetics ; U937 Cells |
مستخلص: | Chalcones are natural compounds described in the literature by its several properties including cytotoxic activity against several tumor types. Considering that the search for new chemotherapeutic agents is still necessary, the aim of this study was to investigate the cytotoxic mechanisms involved in cell death induced by a synthetic chalcone (A23) on different tumor cells. Chalcone A23 reduced the cell viability of twelve tumor cell lines in a concentration and time dependent manner and it was more cytotoxic against acute leukemia cells. Interestingly, the compound was non cytotoxic to normal cells and non-hemolytic to normal red blood cells. Chalcone A23 decreased the expression of cell proliferation marker KI-67 and blocked the G2/M phase in both K562 and Jurkat cell lines. Cells treated with A23 showed morphological features suggestive of apoptosis, the "latter pattern" in agarose gel, the externalization of phosphatidylserine and caspase-3 and PARP cleavage. Chalcone A23 significantly reduced the mitochondrial membrane potential, decreased the expression of anti-apoptotic proteins Bcl-2 and survivin and increased the expression of pro-apoptotic protein Bax, confirming the involvement of the intrinsic pathway. The increased mitochondrial permeability resulted in the release of AIF, cytochrome c and endonuclease G from the mitochondria to the cytosol. In addition, chalcone A23 increased the expression of FasR and induced Bid cleavage, showing the involvement of the extrinsic pathway. Finally, chalcone A23 seems to have a synergic effect with the chemotherapy drugs cytarabine and vincristine. These results suggest that A23 is an interesting compound with strong and selective anti-tumor activity. (Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.) |
فهرسة مساهمة: | Keywords: Acute leukemia; Apoptosis; Cancer cells lines; Chalcone; Cytotoxicity; Death mechanisms |
المشرفين على المادة: | 0 (Chalcones) 0 (Cytotoxins) 0 (Neoplasm Proteins) |
تواريخ الأحداث: | Date Created: 20170615 Date Completed: 20170915 Latest Revision: 20170915 |
رمز التحديث: | 20240628 |
DOI: | 10.1016/j.biochi.2017.06.004 |
PMID: | 28610775 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1638-6183 |
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DOI: | 10.1016/j.biochi.2017.06.004 |