Niclosamide modulates chronic Cryptosporidium-induced ileocecal adenocarcinoma in immunocompromised infected mice via targeting IL-6/IL-22-STAT3 axis

Theodor Bilharz Research Institute

Bibliographic Information

Authors: El-Wakil E.S.; El-Maadawy W.H.; Bayomy A.A.; Shakra M.Y.; Mohamed A.M.A.; Mostafa M.E.S.; Helal H.S.

Journal: Research in Veterinary Science

Publisher: Elsevier B.V.

Publication Date: November 2025

Volume / Issue: Volume 196

Article No.: 105895

ISSN: 345288

DOI: 10.1016/j.rvsc.2025.105895

Scopus: View on Scopus

PubMed: 40967104

Document Type: Article

Authors and Affiliations

El-Wakil E.S., Parasitology Department, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba (P.O. 30), Giza, 12411, Egypt; El-Maadawy W.H., Pharmacology Department, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba (P.O. 30), Giza, 12411, Egypt; Bayomy A.A., Department of Medical Parasitology, Faculty of Medicine, Al-Azhar University, Cairo, Nasr City, Egypt; Shakra M.Y., Department of Medical Parasitology, Faculty of Medicine, Al-Azhar University, New Dameitta, 34517, Egypt; Mohamed A.M.A., Department of Medical Parasitology, Faculty of Medicine, Al-Azhar University, Cairo, Nasr City, Egypt; Mostafa M.E.S., Department of Medical Parasitology, Faculty of Medicine, Al-Azhar University, New Dameitta, 34517, Egypt; Helal H.S., Department of Medical Parasitology, Faculty of Medicine, Al-Azhar University, New Dameitta, 34517, Egypt

Abstract

Cryptosporidiosis, a protozoal disease caused by Cryptosporidium parvum (C. parvum), is a globally emerging waterborne infection leading to moderate to severe diarrhea, particularly in immunocompromised individuals. Emerging evidence proposes a potential correlation between chronic infection and digestive cancers, though the underlying mechanisms remain unclear. Therapeutic options are minimal, with nitazoxanide (NTZ) being the only drug available, despite its constrained effectiveness. Niclosamide (NICLO), an anthelmintic drug, exhibits antiparasitic properties and modulates oncogenic signaling pathways, making it a promising candidate for dual therapeutic effects. This study investigated NICLO's efficacy against chronic C. parvum infection and its potential to prevent ileocecal adenocarcinoma development in immunocompromised mice. Mice were immunosuppressed using dexamethasone, infected with C. parvum oocysts, and administered NTZ or NICLO. NICLO administration significantly reduced parasite burden by 90 %, restored histopathological alterations, and suppressed C. parvum-induced inflammation, as evidenced by suppressed IL-6 and IL-22 levels and STAT3 activation. NICLO also counteracted the antiapoptotic effects of infection by downregulating Bcl-2 and upregulating Bax and cleaved caspase-3 levels. Moreover, NICLO deactivated the Wnt/β-catenin pathway and its target genes (survivin, c-myc, and cyclin D) while elevating p53 levels. These findings highlight NICLO's dual therapeutic potential, which effectively targets C. parvum infection and mitigates its tumorigenic effects by disrupting key signaling pathways involved in ileocecal cancer progression. This study provides novel insights into NICLO's chemotherapeutic efficacy in managing cryptosporidiosis and its associated oncogenic potential. © 2024

Keywords

Cryptosporidium parvum; Ileocecal adenocarcinoma; Intrinsic apoptosis; Niclosamide; STAT3 signaling; Wnt/β-catenin signaling; Adenocarcinoma; Animals; Cryptosporidiosis; Female; Immunocompromised Host; Interleukin-6; Interleukins; Intestinal Neoplasms; Male; Mice; STAT3 Transcription Factor; baculoviral IAP repeat containing protein 5; beta catenin; caspase 3; cyclin D; dexamethasone; interleukin 22; interleukin 6; Myc protein; nitazoxanide; protein Bax; protein bcl 2; protein p53; STAT3 protein; Wnt protein; interleukin derivative; Stat3 protein, mouse; animal tissue; antiapoptotic activity; antitumorigenic activity; apoptosis; Article; cancer growth; canonical Wnt signaling; carcinogenesis; clinical evaluation; controlled study; down regulation; drug efficacy; evidence based practice; histopathology; ileum tissue; inflammation; mouse; nonhuman; oocyst; parasite load; parasitological parameters; protein targeting; real time polymerase chain reaction; small bowel adenocarcinoma; upregulation; Western blotting; animal; complication; drug therapy; genetics; immunocompromised patient; intestine tumor; metabolism; parasitology; prevention and control

Citation Information

Scopus Citations: 3

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