Evidence That Calebin A, a Component of Curcuma Longa Suppresses NF-kappa B Mediated Proliferation, Invasion and Metastasis of Human Colorectal Cancer Induced by TNF-beta (Lymphotoxin)

Buhrmann, Constanze; Popper, Bastian; Kunnumakkara, Ajaikumar B.; Aggarwal, Bharat B. und Shakibaei, Mehdi (2019): Evidence That Calebin A, a Component of Curcuma Longa Suppresses NF-kappa B Mediated Proliferation, Invasion and Metastasis of Human Colorectal Cancer Induced by TNF-beta (Lymphotoxin). In: Nutrients, Bd. 11, Nr. 12, 2904

Abstract

Objective: Natural polyphenol Calebin A has been recently discovered as a novel derivate from turmeric with anti-cancer potential. Pro-inflammatory cytokine TNF-beta (lymphotoxin alpha) is a stimulant for cancer cell malignity via activation of NF-kappa B pathway, also in colorectal cancer (CRC). Here, we investigated the potential of Calebin A to suppress TNF-beta-induced NF-kappa B signalling in CRC. Materials and Methods: Three distinct CRC cell lines (HCT116, RKO, SW480) were treated in monolayer or 3-dimensional alginate culture with TNF-beta, Calebin A, curcumin, BMS-345541, dithiothreitol (DTT) or antisense oligonucleotides-(ASO) against NF-kappa B. Results: Calebin A suppressed dose-dependent TNF-beta-induced CRC cell vitality and proliferation in monolayer culture. Further, in alginate culture, Calebin A significantly suppressed TNF-beta-enhanced colonosphere development, as well as invasion and colony formation of all three CRC cell lines investigated. Calebin A specifically blocked TNF-beta-induced activation and nuclear translocation of p65-NF-kappa B, similar to curcumin (natural NF-kappa B inhibitor), BMS-345541 (specific IKK inhibitor) and ASO-NF-kappa B. Moreover, Immunofluorescence and Immunoblotting showed that Calebin A, similar to curcumin or BMS-345541 suppressed TNF-beta-induced activation and nuclear translocation of p65-NF-kappa B and the transcription of NF-kappa B-promoted biomarkers associated with proliferation, migration and apoptosis, in a dose- and time-dependent manner. Those findings were potentiated by the specific treatment of extracted nuclei with DTT, which abrogated Calebin A-mediated nuclear p65-NF-kappa B-inhibition and restored p65-NF-kappa B-activity in the nucleus. Conclusion: Overall, these results demonstrate, for the first time, that multitargeted Calebin A has an anti-cancer capability on TNF-beta-induced malignities through inhibitory targeting of NF-kappa B activation in the cytoplasm, as well as by suppressing the binding of p65-NF-kappa B to DNA.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch