دورية أكاديمية
أعرض في EDS

Antitumor Activity of Nitazoxanide against Colon Cancers: Molecular Docking and Experimental Studies Based on Wnt/β-Catenin Signaling Inhibition.

التفاصيل البيبلوغرافية
العنوان: Antitumor Activity of Nitazoxanide against Colon Cancers: Molecular Docking and Experimental Studies Based on Wnt/β-Catenin Signaling Inhibition.
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.
References: Nature. 2000 Jul 6;406(6791):86-90. (PMID: 10894547)
Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10747-52. (PMID: 16815967)
Am J Physiol Gastrointest Liver Physiol. 2002 Jul;283(1):G204-11. (PMID: 12065308)
Dev Cell. 2009 Jul;17(1):9-26. (PMID: 19619488)
Cell Death Dis. 2018 Oct 9;9(10):1032. (PMID: 30302016)
J Immunol Methods. 1983 Dec 16;65(1-2):55-63. (PMID: 6606682)
Biochem Biophys Res Commun. 2005 Sep 9;334(4):1365-73. (PMID: 16043125)
Int J Cancer. 2008 Oct 15;123(8):1797-806. (PMID: 18688861)
Gastroenterology. 2010 Jun;138(6):2101-2114.e5. (PMID: 20420949)
Eur J Pharm Sci. 2018 Jan 1;111:526-533. (PMID: 29097304)
Genesis. 2010 Sep;48(9):554-8. (PMID: 20614471)
Nat Rev Drug Discov. 2004 Jun;3(6):479-87. (PMID: 15173837)
Nat Chem Biol. 2018 Jan;14(1):94-101. (PMID: 29083417)
Nat Rev Clin Oncol. 2015 Dec;12(12):732-42. (PMID: 26483297)
Mutat Res. 2014 Oct;768:16-21. (PMID: 25847384)
Cell Calcium. 2005 Sep-Oct;38(3-4):439-46. (PMID: 16099039)
Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1460-5. (PMID: 15665104)
Trends Biochem Sci. 2004 Feb;29(2):95-102. (PMID: 15102436)
RSC Adv. 2020 May 21;10(33):19534-19541. (PMID: 35515454)
Oncol Rep. 2004 Aug;12(2):245-51. (PMID: 15254684)
Expert Rev Anti Infect Ther. 2004 Feb;2(1):43-9. (PMID: 15482170)
Mol Med Rep. 2015 Jul;12(1):192-8. (PMID: 25684678)
Mol Cancer Ther. 2017 Jun;16(6):1187-1198. (PMID: 28336807)
Growth Factors. 2013 Feb;31(1):1-31. (PMID: 23256519)
J Biol Chem. 2006 Jan 13;281(2):1027-38. (PMID: 16293619)
Clin Cancer Res. 2004 Apr 15;10(8):2790-6. (PMID: 15102686)
Chem Biol Interact. 2020 Jun 1;324:109087. (PMID: 32294457)
For Immunopathol Dis Therap. 2010;1(3):155-181. (PMID: 21686046)
Curr Opin Genet Dev. 1999 Feb;9(1):15-21. (PMID: 10072352)
Molecules. 2020 May 28;25(11):. (PMID: 32481682)
Mol Cancer Ther. 2003 Nov;2(11):1215-22. (PMID: 14617795)
Cell Res. 2009 May;19(5):532-45. (PMID: 19365405)
Cancer Gene Ther. 2021 Jun;28(6):590-601. (PMID: 33046820)
Adv Cancer Res. 2002;84:203-29. (PMID: 11883528)
Trends Genet. 2000 Jul;16(7):279-83. (PMID: 10858654)
Cancers (Basel). 2013 Sep 10;5(3):1163-76. (PMID: 24202339)
Int Immunopharmacol. 2012 May;13(1):23-7. (PMID: 22430099)
Trends Pharmacol Sci. 2004 Sep;25(9):471-80. (PMID: 15559249)
Adv Exp Med Biol. 1999;470:23-32. (PMID: 10709671)
Nature. 2012 Jul 18;487(7407):330-7. (PMID: 22810696)
Oncogene. 2004 Oct 14;23(47):7882-92. (PMID: 15361837)
Carbohydr Res. 2019 Dec 1;486:107832. (PMID: 31622868)
J Cell Mol Med. 2012 Aug;16(8):1878-88. (PMID: 22050790)
Mol Cancer Ther. 2013 Sep;12(9):1896-905. (PMID: 23825064)
Methods. 2001 Dec;25(4):402-8. (PMID: 11846609)
Mol Cancer Ther. 2015 Jun;14(6):1504-16. (PMID: 25911689)
Biochem Pharmacol. 2018 Mar;149:174-185. (PMID: 29061341)
Oncogene. 2005 Feb 3;24(6):1098-103. (PMID: 15592505)
Int J Clin Exp Pathol. 2019 Apr 01;12(4):1154-1162. (PMID: 31933930)
Toxicol Mech Methods. 2021 Feb;31(2):138-149. (PMID: 33190582)
CA Cancer J Clin. 2018 Nov;68(6):394-424. (PMID: 30207593)
Drugs. 2007;67(13):1947-67. (PMID: 17722965)
Genes Dev. 2009 Feb 1;23(3):265-77. (PMID: 19204114)
World J Gastrointest Oncol. 2016 Aug 15;8(8):583-91. (PMID: 27574550)
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
الوصف
تدمد:1422-0067
DOI:10.3390/ijms22105213