دورية أكاديمية
The GSTP1/MAPKs/BIM/SMAC modulatory actions of nitazoxanide: Bioinformatics and experimental evidence in subcutaneous solid Ehrlich carcinoma-inoculated mice.
| العنوان: | The GSTP1/MAPKs/BIM/SMAC modulatory actions of nitazoxanide: Bioinformatics and experimental evidence in subcutaneous solid Ehrlich carcinoma-inoculated mice. |
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| المؤلفون: | Imbaby S; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, 41522 Ismailia, Egypt. Electronic address: samar_imbaby@med.suez.edu.eg., Elkholy SE; Department of Clinical Pharmacology, Faculty of Medicine, Port Said University, Port Said, Egypt., Faisal S; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, 41522 Ismailia, Egypt., Abdelmaogood AKK; Department of Clinical and Chemical Pathology, Faculty of Medicine, Suez Canal University, 41522 Ismailia, Egypt., Mehana AE; Department of Zoology, Faculty of Science, Suez Canal University, 41522 Ismailia, Egypt., Mansour BSA; Department of Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, 41522 Ismailia, Egypt., Abd El-Moneam SM; Department of Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, 41522 Ismailia, Egypt., Elaidy SM; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, 41522 Ismailia, Egypt. Electronic address: samah_elaidi@med.suez.edu.eg. |
| المصدر: | Life sciences [Life Sci] 2023 Apr 15; Vol. 319, pp. 121496. Date of Electronic Publication: 2023 Feb 22. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2008->: Amsterdam : Elsevier Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press. |
| مواضيع طبية MeSH: | Caspases*/metabolism , Carcinoma*, Animals ; Mice ; Apoptosis Regulatory Proteins/metabolism ; Glutathione Transferase ; Cytochromes c/metabolism ; Cell Line, Tumor ; Apoptosis ; Fluorouracil/pharmacology ; Fluorouracil/therapeutic use ; Mitochondria/metabolism ; Mitogen-Activated Protein Kinases ; Computational Biology ; Mitochondrial Proteins/metabolism |
| مستخلص: | Aims: Ehrlich ascites carcinoma and its subcutaneous inoculated solid tumour form (SEC) are reliable models for chemotherapeutic molecular targets exploration. Novel chemotherapeutic approaches are identified as molecular targets for intrinsic apoptosis, like the modulation of the second mitochondria-derived activator of caspases (SMAC). SMAC is a physiological substrate of mitogen-activated protein kinases (MAPKs). Glutathione-S-transferase P1 (GSTP1) and its close association with MAPKs play an important role in malignant cell proliferation, metastasis, and resistance to chemotherapeutics. Nitazoxanide (NTZ) is an emerging cancer therapy and its targeted GSTP1 evidence remains a knowledge need. Main Methods: In the present mice-established SEC, the chemotherapeutic roles of oral NTZ (200 mg/kg/day) and 5-fluorouracil (5-FU; 20 mg/kg/day, intraperitoneally) regimens were evaluated by measuring changes in tumour mass, the tumour MAPKs, cytochrome c, Bcl-2 interacting mediator of cell death (BIM), and SMAC signalling pathway in addition to its molecular downstream; caspases 3 and 9. Key Findings: Computational analysis for these target protein interactions showed direct-ordered interactions. After individual therapy with NTZ and 5-FU regimens, the histological architecture of the extracted tumour discs revealed decreases in viable tumour regions with significant necrosis surrounds. These findings were consistent with gross tumour sizes. Each separate regimen lowered the remarkable GSTP1 and elevated the low MAPKs expressions, cytochrome c, BIM, SMAC, and caspases 3, and 9 in EST tissues. Significance: The chemotherapeutic activity of NTZ in SEC was proven. Additionally, NTZ possesses a SMAC modulatory activity that, following thorough research, should be taken into consideration as a chemotherapeutic approach in solid tumours. Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest. (Copyright © 2023 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: 5-Fluorouracil; Glutathione-S-transferase P1 (GSTP1); Molecular docking; Nitazoxanide; Second mitochondria-derived activator of caspases (SMAC) mimetics; Solid Ehrlich carcinoma |
| المشرفين على المادة: | EC 3.4.22.- (Caspases) SOA12P041N (nitazoxanide) 0 (Apoptosis Regulatory Proteins) EC 2.5.1.18 (Glutathione Transferase) 9007-43-6 (Cytochromes c) U3P01618RT (Fluorouracil) EC 2.7.11.24 (Mitogen-Activated Protein Kinases) 0 (Mitochondrial Proteins) |
| تواريخ الأحداث: | Date Created: 20230223 Date Completed: 20230321 Latest Revision: 20230321 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.lfs.2023.121496 |
| PMID: | 36822315 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0631 |
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| DOI: | 10.1016/j.lfs.2023.121496 |