Curcumin, both Histone Deacetylase and p300/CBP‐Specific Inhibitor, Represses the Activity of Nuclear Factor Kappa B and Notch 1 in Raji Cells

• Published in: Basic & clinical pharmacology & toxicology Vol. 101; no. 6; pp. 427 - 433
• Main Authors: Chen, Yan, Shu, Wenxiu, Chen, Weihua, Wu, Qing, Liu, Hongli, Cui, Guohui
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.12.2007; Blackwell
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; CREB-Binding Protein - antagonists & inhibitors; Curcuma longa; Curcumin - administration & dosage; Curcumin - pharmacology; Dose-Response Relationship, Drug; E1A-Associated p300 Protein - antagonists & inhibitors; Gene Expression Regulation - drug effects; Histone Deacetylase 1; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; I-kappa B Proteins - drug effects; I-kappa B Proteins - metabolism; Inhibitory Concentration 50; Leukemia - drug therapy; Leupeptins - pharmacology; Medical sciences; NF-kappa B - antagonists & inhibitors; NF-kappa B - physiology; NF-KappaB Inhibitor alpha; Pharmacology. Drug treatments; Receptor, Notch1 - antagonists & inhibitors; Receptor, Notch1 - physiology; Signal Transduction - drug effects; Transcription Factor RelA - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; Histone deacetylase; Curcumin; Inhibitor; P300 potential; Transcription factor NFκB; In vitro; Biological activity
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/j.1742-7843.2007.00142.x

:  Curcumin, the active chemical of the Asian spice turmeric, exhibits anticancer activity in several human cancer cell lines. We previously have proved that curcumin was a new member of the histone deacetylases (HDAC) inhibitors, while constitutive nuclear factor kappa B (NF‐κB) is believed to be a crucial event for enhanced proliferation and survival of malignant cells. Here, we investigate the effect of curcumin on the activation of NF‐κB signal molecule in Raji cells to explore its relationship with HDACs or p300/CREB binding protein (CBP). Curcumin presented striking proliferation inhibition potency on Raji cells in vitro, with the IC50 value for 24 hr being 25 µmol/l. Significant decreases in the amounts of p300, HDAC1 and HDAC3 were detected after treatment with curcumin. These suppressing effects were more pronounced when the administered dose increased. The protection degradation of HDAC1 and p300 by MG‐132 could be partially reversed by curcumin. Furthermore, curcumin could also prevent degradation of IκBα and inhibit nuclear translocation of the NF‐κB/p65 subunit, as well as expression of Notch 1, induced by tumour necrosis factor‐α. The results suggest that the depressive effect of curcumin on NF‐κB signal transduction pathway may be mediated via the various components of the HDACs and p300/Notch 1 signal molecules, and may represent a new remedy for acute leukaemia.