Celastrol Ameliorates Ulcerative Colitis-Related Colorectal Cancer in Mice via Suppressing Inflammatory Responses and Epithelial-Mesenchymal Transition

Frontiers in Pharmacology
Lianjie LinChangqing Zheng

Abstract

Celastrol, also named as tripterine, is a pharmacologically active ingredient extracted from the root of traditional Chinese herb Tripterygium wilfordii Hook F with potent anti-inflammatory and anti-tumor activities. In the present study, we investigated the effects of celastrol on ulcerative colitis-related colorectal cancer (UC-CRC) as well as CRC in vivo and in vitro and explored its underlying mechanisms. UC-CRC model was induced in C57BL/6 mice by administration of azoxymethane (AOM) and dextran sodium sulfate (DSS). Colonic tumor xenograft models were developed in BALB/c-nu mice by subcutaneous injection with HCT116 and HT-29 cells. Intragastric administration of celastrol (2 mg/kg/d) for 14 weeks significantly increased the survival ratio and reduced the multiplicity of colonic neoplasms compared with AOM/DSS model mice. Mechanically, celastrol treatment significantly prevented AOM/DSS-induced up-regulation of expression levels of oncologic markers including mutated p53 and phospho-p53, β-catenin and proliferating cell nuclear antigen (PCNA). In addition, treatment with celastrol inhibited inflammatory responses, as indicated by the decrease of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, down-reg...Continue Reading

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Citations

Jan 26, 2017·Frontiers in Immunology·Ping KeChong Liu
Dec 17, 2019·Current Pharmaceutical Design·Fan CaoHai-Feng Pan
Aug 17, 2019·Frontiers in Pharmacology·Lorena Avila-CarrascoGuadalupe González Mateo
Feb 13, 2019·Frontiers in Oncology·Li-Na XuXiao-Jian Yan
Jul 1, 2017·Frontiers in Medicine·Rita CascãoLuis F Moita
Dec 29, 2020·Frontiers in Pharmacology·Jinfeng ShiChaomei Fu

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Methods Mentioned

BETA
xenograft
xenografts
Protein Assay
electrophoresis
ELISA
nuclear translocation

Software Mentioned

GraphPad Prism
GraphPad

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