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

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-kappa B (NF-kappa B) activity. Parthenolide (PT) inhibits NF-kappa B and exerts promising anticancer effects by promoting apoptosis. The present investigated the antitumor effects of balsalazide, combined with PT, on NF-kappa B 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-kappa B p65 subunit and the phosphorylation of inhibitor of NF-kappa B. Moreover, PT and balsalazide dramatically enhanced NF-kappa B 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.