Balsalazide Potentiates Parthenolide-Mediated Inhibition of Nuclear Factor-kappaB Signaling in HCT116 Human Colorectal Cancer Cells.
- Author:
Hyun Young KIM
1
;
Se Lim KIM
;
Young Ran PARK
;
Yu Chuan LIU
;
Seung Young SEO
;
Seong Hun KIM
;
In Hee KIM
;
Seung Ok LEE
;
Soo Teik LEE
;
Sang Wook KIM
Author Information
- Publication Type:Original Article
- Keywords: Balsalazide; Parthenolide; NF-kappaB; Apoptosis; Colorectal neoplasms
- MeSH: Apoptosis; Blotting, Western; Caspase 3; Cell Cycle; Cell Death; Cell Line; Colorectal Neoplasms*; Cytochromes c; HCT116 Cells; Humans; Inflammatory Bowel Diseases; NF-kappa B; Phosphorylation
- From:Intestinal Research 2015;13(3):233-241
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/AIMS: Balsalazide is an anti-inflammatory drug used in the treatment of inflammatory bowel disease. Balsalazide can reduce inflammatory responses via several mechanisms, including inhibition of nuclear factor-kappaB (NF-kappaB) activity. Parthenolide (PT) inhibits NF-kappaB and exerts promising anticancer effects by promoting apoptosis. The present investigated the antitumor effects of balsalazide, combined with PT, on NF-kappaB in a representative human colorectal carcinoma cell line, HCT116. METHODS: We counted cells and conducted annexin-V assays and cell cycle analysis to measure apoptotic cell death. Western blotting was used investigate the levels of proteins involved in apoptosis. RESULTS: PT and balsalazide produced synergistic anti-proliferative effects and induced apoptotic cell death. The combination of balsalazide and PT markedly suppressed nuclear translocation of the NF-kappaB p65 subunit and the phosphorylation of inhibitor of NF-kappaB. Moreover, PT and balsalazide dramatically enhanced NF-kappaB p65 phosphorylation. Apoptosis, through the mitochondrial pathway, was confirmed by detecting effects on Bcl-2 family members, cytochrome c release, and activation of caspase-3 and -8. CONCLUSIONS: Combination treatment with PT and balsalazide may offer an effective strategy for the induction of apoptosis in HCT116 cells.
