The chemopreventive effect of withaferin A on spontaneous and inflammation-associated colon carcinogenesis models
| Autor: | Murali K. Ankem, Arun Sharma, Becca V. Baby, Deeksha Pal, Houda Alatassi, Ashish Tyagi, Nisha Dahiya, Khafateh Youssef, Balaji Chandrasekaran, Chendil Damodaran, Venkatesh Kolluru |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Cancer Research Carcinogenesis Colon Adenomatous polyposis coli Mice Transgenic Inflammation Ileum Tumor initiation Chemoprevention Jejunum Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Anticarcinogenic Agents Withanolides biology Azoxymethane business.industry General Medicine digestive system diseases Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure chemistry Withaferin A 030220 oncology & carcinogenesis Colonic Neoplasms Cancer research biology.protein Female Tumor necrosis factor alpha medicine.symptom business |
| Zdroj: | Carcinogenesis. 39:1537-1547 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgy109 |
| Popis: | Chemopreventive effects and associated mechanisms of withaferin A (WA) against intestinal and colon carcinogenesis remain unknown. We investigated the chemopreventive effect of WA on transgenic adenomatous polyposis coli (APC(Min/+)) mouse and chemically induced azoxymethane/dextran sodium sulfate (AOM/DSS) models of intestinal and colon carcinogenesis. Oral WA administration (4 and 3 mg/kg) inhibited tumor initiation and progression of intestinal polyps formation in APC(Min/+) mice and colon carcinogenesis in the AOM/DSS mouse model. WA-administered mice showed a significant reduction in both number [duodenum, 33% (P > 0.05); jejunum, 32% (P < 0.025); ileum, 43% ( P < 0.001); and colon 59% (P < 0.01] and size of polyps in APC(Min/+) mice compared with the respective controls. Similarly, tumor multiplicity was significantly reduced (P < 0.05) in the colon of WA-administered AOM/DSS mice. Pathological analysis showed reduced adenomas and tissue inflammation in WA-administered mouse models. Molecular studies suggested that WA inhibited the expression of inflammatory (interluekin-6, tumor necrosis factor-alpha and cyclooxygenase-2), pro-survival (pAKT, Notch1 and NF-κB) markers in APC(Min/+) and AOM/DSS models. The results suggest that WA is a potent agent for preventing colon carcinogenesis and further investigation is required to show clinical utility of the agent. |
| Databáze: | OpenAIRE |
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