Balsalazide Potentiates Parthenolide-Mediated Inhibition of Nuclear Factor-κB Signaling in HCT116 Human Colorectal Cancer Cells

• Main Authors: Hyun-Young Kim, 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
• Format: Article
• Language: English
• Published: Korean Association for the Study of Intestinal Diseases 2015-07-01
• Series: Intestinal Research
• Subjects: Balsalazide; Parthenolide; NF-κB; Apoptosis; Colorectal neoplasms
• Online Access: http://www.irjournal.org/upload/pdf/ir-13-233.pdf

Background/AimsBalsalazide 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-κB (NF-κB) activity. Parthenolide (PT) inhibits NF-κB and exerts promising anticancer effects by promoting apoptosis. The present investigated the antitumor effects of balsalazide, combined with PT, on NF-κB in a representative human colorectal carcinoma cell line, HCT116.MethodsWe 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.ResultsPT 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-κB p65 subunit and the phosphorylation of inhibitor of NF-κB. Moreover, PT and balsalazide dramatically enhanced NF-κB 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.ConclusionsCombination treatment with PT and balsalazide may offer an effective strategy for the induction of apoptosis in HCT116 cells.