Nifuroxazide Mitigates Angiogenesis in Ehlrich’s Solid Carcinoma: Molecular Docking, Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling

Nifuroxazide is an antidiarrheal medication that has promising anticancer activity against diverse types of tumors. The present study tested the anticancer activity of nifuroxazide against Ehrlich’s mammary carcinoma grown in vivo. Furthermore, we investigated the effect of nifuroxazide on IL-6/jak2...

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Autores principales:	Mohamed El-Sherbiny, Rehab M. El-Sayed, Mohamed A. Helal, Afaf T. Ibrahiem, Hoda S. Elmahdi, Mohamed Ahmed Eladl, Shymaa E. Bilay, Asma M. Alshahrani, Mona K. Tawfik, Ziad E. Hamed, Amany O. Mohamed, Sawsan A. Zaitone
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	angiogenesis bioinformatics Ehrlich’s solid tumors molecular docking IL-6/Jak2/STAT3 signaling nifuroxazide Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/93dbed2281304f2aba06c3ade34e5b39
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spelling	oai:doaj.org-article:93dbed2281304f2aba06c3ade34e5b392021-11-25T18:27:53ZNifuroxazide Mitigates Angiogenesis in Ehlrich’s Solid Carcinoma: Molecular Docking, Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling10.3390/molecules262268581420-3049https://doaj.org/article/93dbed2281304f2aba06c3ade34e5b392021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6858https://doaj.org/toc/1420-3049Nifuroxazide is an antidiarrheal medication that has promising anticancer activity against diverse types of tumors. The present study tested the anticancer activity of nifuroxazide against Ehrlich’s mammary carcinoma grown in vivo. Furthermore, we investigated the effect of nifuroxazide on IL-6/jak2/STAT3 signaling and the possible impact on tumor angiogenesis. The biological study was supported by molecular docking and bioinformatic predictions for the possible effect of nifuroxazide on this signaling pathway. Female albino mice were injected with Ehrlich carcinoma cells to produce Ehrlich’s solid tumors (ESTs). The experimental groups were as follows: EST control, EST + nifuroxazide (5 mg/kg), and EST + nifuroxazide (10 mg/kg). Nifuroxazide was found to reduce tumor masses (730.83 ± 73.19 and 381.42 ± 109.69 mg vs. 1099.5 ± 310.83) and lessen tumor pathologies. Furthermore, nifuroxazide downregulated IL-6, TNF-α, NFk-β, angiostatin, and Jak2 proteins, and it also reduced tumoral VEGF, as indicated by ELISA and immunohistochemical analysis. Furthermore, nifuroxazide dose-dependently downregulated STAT3 phosphorylation (60% and 30% reductions, respectively). Collectively, the current experiment shed light on the antitumor activity of nifuroxazide against mammary solid carcinoma grown in vivo. The antitumor activity was at least partly mediated by inhibition of IL-6/Jak2/STAT3 signaling that affected angiogenesis (low VEGF and high angiostatin) in the EST. Therefore, nifuroxazide might be a promising antitumor medication if appropriate human studies will be conducted.Mohamed El-SherbinyRehab M. El-SayedMohamed A. HelalAfaf T. IbrahiemHoda S. ElmahdiMohamed Ahmed EladlShymaa E. BilayAsma M. AlshahraniMona K. TawfikZiad E. HamedAmany O. MohamedSawsan A. ZaitoneMDPI AGarticleangiogenesisbioinformaticsEhrlich’s solid tumorsmolecular dockingIL-6/Jak2/STAT3 signalingnifuroxazideOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6858, p 6858 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	angiogenesis bioinformatics Ehrlich’s solid tumors molecular docking IL-6/Jak2/STAT3 signaling nifuroxazide Organic chemistry QD241-441
spellingShingle	angiogenesis bioinformatics Ehrlich’s solid tumors molecular docking IL-6/Jak2/STAT3 signaling nifuroxazide Organic chemistry QD241-441 Mohamed El-Sherbiny Rehab M. El-Sayed Mohamed A. Helal Afaf T. Ibrahiem Hoda S. Elmahdi Mohamed Ahmed Eladl Shymaa E. Bilay Asma M. Alshahrani Mona K. Tawfik Ziad E. Hamed Amany O. Mohamed Sawsan A. Zaitone Nifuroxazide Mitigates Angiogenesis in Ehlrich’s Solid Carcinoma: Molecular Docking, Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling
description	Nifuroxazide is an antidiarrheal medication that has promising anticancer activity against diverse types of tumors. The present study tested the anticancer activity of nifuroxazide against Ehrlich’s mammary carcinoma grown in vivo. Furthermore, we investigated the effect of nifuroxazide on IL-6/jak2/STAT3 signaling and the possible impact on tumor angiogenesis. The biological study was supported by molecular docking and bioinformatic predictions for the possible effect of nifuroxazide on this signaling pathway. Female albino mice were injected with Ehrlich carcinoma cells to produce Ehrlich’s solid tumors (ESTs). The experimental groups were as follows: EST control, EST + nifuroxazide (5 mg/kg), and EST + nifuroxazide (10 mg/kg). Nifuroxazide was found to reduce tumor masses (730.83 ± 73.19 and 381.42 ± 109.69 mg vs. 1099.5 ± 310.83) and lessen tumor pathologies. Furthermore, nifuroxazide downregulated IL-6, TNF-α, NFk-β, angiostatin, and Jak2 proteins, and it also reduced tumoral VEGF, as indicated by ELISA and immunohistochemical analysis. Furthermore, nifuroxazide dose-dependently downregulated STAT3 phosphorylation (60% and 30% reductions, respectively). Collectively, the current experiment shed light on the antitumor activity of nifuroxazide against mammary solid carcinoma grown in vivo. The antitumor activity was at least partly mediated by inhibition of IL-6/Jak2/STAT3 signaling that affected angiogenesis (low VEGF and high angiostatin) in the EST. Therefore, nifuroxazide might be a promising antitumor medication if appropriate human studies will be conducted.
format	article
author	Mohamed El-Sherbiny Rehab M. El-Sayed Mohamed A. Helal Afaf T. Ibrahiem Hoda S. Elmahdi Mohamed Ahmed Eladl Shymaa E. Bilay Asma M. Alshahrani Mona K. Tawfik Ziad E. Hamed Amany O. Mohamed Sawsan A. Zaitone
author_facet	Mohamed El-Sherbiny Rehab M. El-Sayed Mohamed A. Helal Afaf T. Ibrahiem Hoda S. Elmahdi Mohamed Ahmed Eladl Shymaa E. Bilay Asma M. Alshahrani Mona K. Tawfik Ziad E. Hamed Amany O. Mohamed Sawsan A. Zaitone
author_sort	Mohamed El-Sherbiny
title	Nifuroxazide Mitigates Angiogenesis in Ehlrich’s Solid Carcinoma: Molecular Docking, Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling
title_short	Nifuroxazide Mitigates Angiogenesis in Ehlrich’s Solid Carcinoma: Molecular Docking, Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling
title_full	Nifuroxazide Mitigates Angiogenesis in Ehlrich’s Solid Carcinoma: Molecular Docking, Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling
title_fullStr	Nifuroxazide Mitigates Angiogenesis in Ehlrich’s Solid Carcinoma: Molecular Docking, Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling
title_full_unstemmed	Nifuroxazide Mitigates Angiogenesis in Ehlrich’s Solid Carcinoma: Molecular Docking, Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling
title_sort	nifuroxazide mitigates angiogenesis in ehlrich’s solid carcinoma: molecular docking, bioinformatic and experimental studies on inhibition of il-6/jak2/stat3 signaling
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/93dbed2281304f2aba06c3ade34e5b39
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Nifuroxazide Mitigates Angiogenesis in Ehlrich’s Solid Carcinoma: Molecular Docking, Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling

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