دورية أكاديمية
Antitumor Activity of Nitazoxanide against Colon Cancers: Molecular Docking and Experimental Studies Based on Wnt/β-Catenin Signaling Inhibition.
العنوان: | Antitumor Activity of Nitazoxanide against Colon Cancers: Molecular Docking and Experimental Studies Based on Wnt/β-Catenin Signaling Inhibition. |
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المؤلفون: | Abd El-Fadeal NM; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., Nafie MS; Chemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt., K El-Kherbetawy M; Department of Pathology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., El-Mistekawy A; Department of Internal Medicine, Gastroenterology Division, Faculty of Medicine, Al-azhar University, Cairo 11651, Egypt., Mohammad HMF; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.; Central Laboratory, Center of Excellence in Molecular and Cellular Medicine (CEMCM), Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., Elbahaie AM; Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., Hashish AA; Basic Medical Sciences Department, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.; Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., Alomar SY; Doping Research Chair, Department of Zoology, College of Science, King Saud University, Riyadh 11495, Saudi Arabia., Aloyouni SY; Health Sciences Research Center, Princess Nourah bint Abdulrahman University, Riyadh 36285, Saudi Arabia., El-Dosoky M; Department of Neuroscience Technology, College of Applied Medical Sciences in Jubail, Imam Abdulrahman Bin Faisal University, Jubail 35816, Saudi Arabia., Morsy KM; Department of Anesthesia Technology, College of Applied Medical Science in Jubail, Imam Abdulrahman Bin Faisal University, Jubail 35816, Saudi Arabia., Zaitone SA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk 714, Saudi Arabia. |
المصدر: | International journal of molecular sciences [Int J Mol Sci] 2021 May 14; Vol. 22 (10). Date of Electronic Publication: 2021 May 14. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, [2000- |
مواضيع طبية MeSH: | Antiparasitic Agents/*pharmacology , Colonic Neoplasms/*drug therapy , Nitro Compounds/*pharmacology , Thiazoles/*pharmacology , Wnt Signaling Pathway/*drug effects, Animals ; Antiparasitic Agents/chemistry ; Apoptosis/drug effects ; Apoptosis/genetics ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Gene Expression Regulation, Neoplastic/drug effects ; Glycogen Synthase Kinase 3 beta/metabolism ; HCT116 Cells ; Humans ; Male ; Mice ; Molecular Docking Simulation ; Nitro Compounds/chemistry ; Proliferating Cell Nuclear Antigen/immunology ; Proliferating Cell Nuclear Antigen/metabolism ; Thiazoles/chemistry ; Xenograft Model Antitumor Assays ; beta Catenin/metabolism |
مستخلص: | In colon cancer, wingless (Wnt)/β-catenin signaling is frequently upregulated; however, the creation of a molecular therapeutic agent targeting this pathway is still under investigation. This research aimed to study how nitazoxanide can affect Wnt/β-catenin signaling in colon cancer cells (HCT-116) and a mouse colon cancer model. Our study included 2 experiments; the first was to test the cytotoxic activity of nitazoxanide in an in vitro study on a colon cancer cell line (HCT-116) versus normal colon cells (FHC) and to highlight the proapoptotic effect by MTT assay, flow cytometry and real-time polymerase chain reaction (RT-PCR). The second experiment tested the in vivo cytotoxic effect of nitazoxanide against 1,2-dimethylhydrazine (DMH) prompted cancer in mice. Mice were grouped as saline, DMH control and DMH + nitazoxanide [100 or 200 mg per kg]. Colon levels of Wnt and β-catenin proteins were assessed by Western blotting while proliferation was measured via immunostaining for proliferating cell nuclear antigen (PCNA). Treating HCT-116 cells with nitazoxanide (inhibitory concentration 50 (IC50) = 11.07 µM) revealed that it has a more cytotoxic effect when compared to 5-flurouracil (IC50 = 11.36 µM). Moreover, it showed relatively high IC50 value (non-cytotoxic) against the normal colon cells. Nitazoxanide induced apoptosis by 15.86-fold compared to control and arrested the cell cycle. Furthermore, nitazoxanide upregulated proapoptotic proteins (P53 and BAX) and caspases but downregulated BCL-2. Nitazoxanide downregulated Wnt/β-catenin/glycogen synthase kinase-3β (GSK-3β) signaling and PCNA staining in the current mouse model. Hence, our findings highlighted the cytotoxic effect of nitazoxanide and pointed out the effect on Wnt/β-catenin/GSK-3β signaling. |
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معلومات مُعتمدة: | none Deanship of Scientific Research, King Saud University; Fast track the Deanship of Scientific Research at princess Nourah bint Abdulrahman University |
فهرسة مساهمة: | Keywords: PCNA; Wnt/β-catenin signaling; apoptosis; molecular docking; mouse colon cancer; nitazoxanide |
المشرفين على المادة: | 0 (Antiparasitic Agents) 0 (CTNNB1 protein, human) 0 (Nitro Compounds) 0 (Proliferating Cell Nuclear Antigen) 0 (Thiazoles) 0 (beta Catenin) EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) SOA12P041N (nitazoxanide) |
تواريخ الأحداث: | Date Created: 20210602 Date Completed: 20210702 Latest Revision: 20240402 |
رمز التحديث: | 20240402 |
مُعرف محوري في PubMed: | PMC8156814 |
DOI: | 10.3390/ijms22105213 |
PMID: | 34069111 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1422-0067 |
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DOI: | 10.3390/ijms22105213 |