Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling

Kim,Se  Lim; Liu,Yu  Chuan; Seo,Seung  Young; Kim,Seong  Hun; Kim,In  Hee; Lee,Seung  Ok; Lee,Soo  Teik; Kim,Dae‑Ghon; Kim,Sang  Wook

doi:10.3892/ol.2015.3017

Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling

Authors:
- Se Lim Kim
- Yu Chuan Liu
- Seung Young Seo
- Seong Hun Kim
- In Hee Kim
- Seung Ok Lee
- Soo Teik Lee
- Dae‑Ghon Kim
- Sang Wook Kim
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Affiliations: Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561‑712, Republic of Korea
Published online on: March 6, 2015 https://doi.org/10.3892/ol.2015.3017
Pages: 2135-2142

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Abstract

Recently, the nuclear factor (NF)‑κB inhibitor parthenolide (PT) was identified as a promising anticancer agent for the promotion of cancer cell apoptosis. Additionally, our previous study demonstrated that PT administration suppresses tumor growth in a xenograft model of colorectal cancer cells via regulation of the B‑cell lymphoma‑2 (Bcl-2) family. However, the role of PT in the development of colitis‑associated colon cancer (CAC) is poorly understood. Therefore, the aim of the present study was to investigate the effects of PT administration on CAC using a murine model. Azoxymethane (AOM) and dextran sulfate sodium (DSS) were administered to induce experimental CAC in the following three groups of treated mice: i) AOM and DSS plus vehicle; ii) AOM, DSS and 2 mg/kg PT; and iii) AOM, DSS and 4 mg/kg PT. It was demonstrated that the histological acuteness of AOM/DSS‑induced CAC was significantly reduced following the administration of PT, resulting in decreased NF‑κB p65 expression levels via a blockade of phosphorylation and subsequent degradation of inhibitor of κB‑α (IκBα). Furthermore, PT administration appeared to enhance the process of carcinogenesis via the downregulation of the antiapoptotic proteins Bcl‑2 and Bcl‑extra large, mediated by inhibition of NF‑κB activation. Apoptosis and caspase‑3 expression were markedly increased in the PT‑treated group. These findings indicate that PT inhibits IκBα phosphorylation and NF‑κB activation, resulting in the initiation of apoptosis and the eventual suppression of CAC development. The beneficial effects of PT treatment observed in the experimental CAC model indicate the potential chemopreventive and therapeutic role of PT in CAC.

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