title: Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling.
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.
authors.affiliation: Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea ; Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea.
authors.forename: Se Lim
authors.initials: SL
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea ; Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea.
authors.forename: Yu Chuan
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea ; Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea.
authors.forename: Seung Young
authors.initials: SY
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea ; Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea.
authors.forename: Seong Hun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea ; Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea.
authors.forename: In Hee
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea ; Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea.
authors.forename: Seung Ok
authors.initials: SO
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea ; Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea.
authors.forename: Soo Teik
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea ; Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea.
authors.forename: Dae-Ghon
authors.initials: DG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea ; Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeollabuk-do 561-712, Republic of Korea.
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Kim
keywords: apoptosis; colitis-associated colon cancer; nuclear factor-κB; parthenolide