Artemisinin and its derivatives prevent Helicobacter pylori-induced gastric carcinogenesis via inhibition of NF-κB signaling.
Background: Gastric cancer has a high morbidity and is a leading cause of cancer-related mortality worldwide. Helicobacter pylori (H. pylori) infection is commonly found in the early stage of gastric cancer pathogenesis, which induces chronic gastritis. Artemisinin (ART) and its derivatives (ARTS, a...
| Publicado en: | Phytomedicine Vol. 63 |
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| Autores principales: | , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Elsevier GmbH, Urban & Fischer Verlag
Oct2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=139562842&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 139562842 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09447113 NXH jtl: Phytomedicine issn: 09447113 maglogo: N pubinfo: dt: Oct2019 vid: 63 pid: 24997 pub: Elsevier GmbH, Urban & Fischer Verlag place: London, <Blank> artinfo: ui: 139562842 139562842 NLM31280140 139562842 10.1016/j.phymed.2019.152968 NLM31280140 139562842 ppct: 1 formats: tig: atl: Artemisinin and its derivatives prevent Helicobacter pylori-induced gastric carcinogenesis via inhibition of NF-κB signaling. aug: au: Su, Tao Li, Fangyuan Guan, Jiaji Liu, Linxin Huang, Ping Wang, Ying Qi, Xiaoxiao Liu, Zhongqiu Lu, Linlin Wang, Dawei affil: Shunde Hospital of Guangzhou University of Chinese Medicine, Shunde, Guangdong, China sug: subj: Helicobacter Infections Complications Antineoplastic Agents Pharmacodynamics Helicobacter Pylori Drug Effects Stomach Neoplasms Prevention and Control Antimalarials Pharmacodynamics NF-kappa B Metabolism Reactive Oxygen Species Metabolism Microbial Culture and Sensitivity Tests Stomach Neoplasms Microbiology Animals Cytokines Metabolism Stomach Neoplasms Pathology Bacterial Physiology Drug Effects Helicobacter Pylori Cell Line, Tumor Mice Animal Studies ab: Background: Gastric cancer has a high morbidity and is a leading cause of cancer-related mortality worldwide. Helicobacter pylori (H. pylori) infection is commonly found in the early stage of gastric cancer pathogenesis, which induces chronic gastritis. Artemisinin (ART) and its derivatives (ARTS, artesunate and DHA, dihydroartemisinin), a new class of potent antimalarials, have been reported to exert both preventive and anti-gastric cancer effects. However, the underlying mechanisms of the chemopreventive effects of ART and its derivatives in H. pylori infection induced-gastric cancer are not fully elucidated.Purpose: We investigated the effects of H. pylori infection in gastric cancer; and the preventive mechanisms of ART, ARTS and DHA.Methods: The H. pylori growth was determined by the broth macro-dilution method, and its adhesion to gastric cancer cells was evaluated by using the urease assay. The protein and mRNA levels, reactive oxygen species (ROS) production, as well as the production of inflammatory cytokines were evaluated by Western blot, real-time PCR, flow cytometry and ELISA, respectively. Moreover, an in vivo MNU (N-methyl-N-nitroso-urea) and H. pylori-induced gastric adenocarcinoma mouse model was established for the investigation of the cancer preventive effects of ART and its derivaties, and the underlying mechanisms of action.Results: ART, DHA and ARTS inhibited the growth of H. pylori and gastric cancer cells,suppressed H. pylori adhesion to the gastric cancer cells, and reduced the H. pylori-enhanced ROS production. Moreover, ART, DHA and ARTS significantly reduced tumor incidence, number of tumor nodules and tumor size in the mouse model. Among these three compounds, DHA exerted the most potent chemopreventive effect. Mechanistic studies showed that ART and its derivatives potently inhibited the NF-κB activation.Conclusion: ART, DHA and ARTS have potent preventive effects in H. pylori-induced gastric carcinogenesis. These effects are, at least in part, attributed to the inhibition of NF-κB signaling pathway. Our findings provide a molecular justification of using ART and its derivatives for the prevention and treatment of gastric cancer. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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