دورية أكاديمية
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Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line.

التفاصيل البيبلوغرافية
العنوان: Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line.
المؤلفون: Molatlhegi RP; Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, RSA., Phulukdaree A; Department of Physiology, School of Medicine, University of Pretoria, Pretoria, RSA., Anand K; Department of Chemistry, Faculty of Applied Sciences, Durban University of Technology, Durban, RSA., Gengan RM; Department of Chemistry, Faculty of Applied Sciences, Durban University of Technology, Durban, RSA., Tiloke C; Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, RSA., Chuturgoon AA; Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, RSA.
المصدر: PloS one [PLoS One] 2015 Jul 02; Vol. 10 (7), pp. e0129874. Date of Electronic Publication: 2015 Jul 02 (Print Publication: 2015).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Gene Expression Regulation, Neoplastic*, Carbazoles/*pharmacology , Cytotoxins/*pharmacology , Epithelial Cells/*drug effects , Pentanones/*pharmacology, Apoptosis/drug effects ; Carbazoles/chemical synthesis ; Caspases/genetics ; Caspases/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cytotoxins/chemical synthesis ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; HSP70 Heat-Shock Proteins/antagonists & inhibitors ; HSP70 Heat-Shock Proteins/genetics ; HSP70 Heat-Shock Proteins/metabolism ; Humans ; Lipid Peroxidation ; NF-E2-Related Factor 2/antagonists & inhibitors ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress/drug effects ; Pentanones/chemical synthesis ; Phosphatidylserines/metabolism ; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Reactive Oxygen Species/agonists ; Reactive Oxygen Species/metabolism ; Respiratory Mucosa/drug effects ; Respiratory Mucosa/metabolism ; Respiratory Mucosa/pathology ; Signal Transduction ; Superoxide Dismutase/antagonists & inhibitors ; Superoxide Dismutase/genetics ; Superoxide Dismutase/metabolism ; Tumor Suppressor Protein p53/antagonists & inhibitors ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; bcl-2-Associated X Protein/agonists ; bcl-2-Associated X Protein/genetics ; bcl-2-Associated X Protein/metabolism
مستخلص: Increased death rates due to lung cancer have necessitated the search for potential novel anticancer compounds such as carbazole derivatives. Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity. The study investigated the ability of the novel carbazole compound (Z)-4-[9-ethyl-9aH-carbazol-3-yl) amino] pent-3-en-2-one (ECAP) to induce cytotoxicity of lung cancer cells and its mechanism of action. ECAP was synthesized as a yellow powder with melting point of 240-247 °C. The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lipid peroxidation and comet assays were used to assess the cytotoxic effect of the compound on A549 lung cancer cells. Protein expression was determined using western blots, apoptosis was measured by luminometry (caspase-3/7, -8 and -9) assay and flow cytometry was used to measure phosphatidylserine (PS) externalisation. ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD), Hsp70 (p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen species (ROS) production. This resulted in DNA damage (p < 0.0001), up-regulation of Bax expression and caspase activity and induction of apoptosis in lung cancer cells. The results show the anticancer potential of ECAP on lung cancer.
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المشرفين على المادة: 0 (4-(9-ethyl-9aH-carbazol-3-yl)amino)pent-3-en-2-one)
0 (BAX protein, human)
0 (BCL2 protein, human)
0 (Carbazoles)
0 (Cytotoxins)
0 (HSP70 Heat-Shock Proteins)
0 (NF-E2-Related Factor 2)
0 (NFE2L2 protein, human)
0 (Pentanones)
0 (Phosphatidylserines)
0 (Proto-Oncogene Proteins c-bcl-2)
0 (Reactive Oxygen Species)
0 (Tumor Suppressor Protein p53)
0 (bcl-2-Associated X Protein)
EC 1.15.1.1 (Superoxide Dismutase)
EC 3.4.22.- (Caspases)
تواريخ الأحداث: Date Created: 20150703 Date Completed: 20160412 Latest Revision: 20240714
رمز التحديث: 20240714
مُعرف محوري في PubMed: PMC4489925
DOI: 10.1371/journal.pone.0129874
PMID: 26134408
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0129874