Thymoquinone attenuates tumor growth in ApcMin mice by interference with Wnt-signaling

Molecular Cancer

Research

Robin Ristl¹  Vineeta Khare²  Melanie Borgmann²  Christoph Gasche²  Christoph Campregher²  Rayko Evstatiev²  Kristine Jimenez²  Michaela Lang²  Kyle W Dammann²  Manuela Jambrich²  Georg Oberhuber³ 

[1] Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Medical Statistics, Medical University of Vienna, Vienna, Austria;Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria;Christian Doppler Laboratory for Molecular Cancer Chemoprevention, Medical University of Vienna, Vienna, Austria;Pathology Ueberlingen, Ueberlingen, Germany;

关键词: Nigella sativa;    Thymoquinone;    Chemoprevention;    Colon cancer;    Familial adenomatous polyposis;   

DOI  :  10.1186/1476-4598-12-41

 received in 2013-01-11, accepted in 2013-05-07,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundPatients with familial adenomatous polyposis (FAP) are at increased risk for the development of colorectal cancer. Surgery and chemoprevention are the most effective means to prevent cancer development. Thymoquinone (TQ) is considered the main compound of the volatile Nigella sativa seed oil and has been reported to possess anticarcinogenic properties. In this study we evaluated the chemopreventive properties of TQ in a mouse model of FAP.MethodsAPCMin mice were fed with chow containing 37.5 mg/kg or 375 mg/kg TQ for 12 weeks. H&E stained intestine tissue sections were assessed for tumor number, localization, size, and grade. Immunohistochemistry for β-catenin, c-myc, Ki-67 and TUNEL-staining was performed to investigate TQ’s effect on major colorectal cancer pathways. TQ’s impact on GSK-3β and β-catenin were studied in RKO cells.Results375 mg/kg but not 37.5 mg/kg TQ decreased the number of large polyps in the small intestine of APCMin mice. TQ induced apoptosis in the neoplastic tissue but not in the normal mucosa. Furthermore, upon TQ treatment, β-catenin was retained at the membrane and c-myc decreased in the nucleus, which was associated with a reduced cell proliferation in the villi. In vitro, TQ activated GSK-3β, which induced membranous localization of β-catenin and reduced nuclear c-myc expression.ConclusionsIn summary, TQ interferes with polyp progression in ApcMin mice through induction of tumor-cell specific apoptosis and by modulating Wnt signaling through activation of GSK-3β. Nigella sativa oil (or TQ) might be useful as nutritional supplement to complement surgery and chemoprevention in FAP.

【 授权许可】

Unknown   
© Lang et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.