Curcumin, both histone deacetylase and p300/CBP-specific inhibitor, represses the activity of nuclear factor kappa B and Notch 1 in Raji cells.
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-kappaB) 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-kappaB 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 IC(50) value for 24 hr being 25 micromol/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 I kappaB alpha and inhibit nuclear translocation of the NF-kappaB/p65 subunit, as well as expression of Notch 1, induced by tumour necrosis factor-alpha. The results suggest that the depressive effect of curcumin on NF-kappaB 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.
Chen
Yan
Y
Department of Haematology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. yanchen@public.wh.hb.cn
Shu
Wenxiu
W
Chen
Weihua
W
Wu
Qing
Q
Liu
Hongli
H
Cui
Guohui
G
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D050882:CREB-Binding Protein / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D050881:E1A-Associated p300 Protein / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006801:Humans; D020672:I-kappa B Proteins / Q000187:drug effects / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy; D007976:Leupeptins / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099186:Histone Deacetylase 3
D000970:Antineoplastic Agents; D050882:CREB-Binding Protein; D003474:Curcumin; D050881:E1A-Associated p300 Protein; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D020672:I-kappa B Proteins; D007976:Leupeptins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D051881:Receptor, Notch1; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000099186:Histone Deacetylase 3; C000606204:NFKBIA protein, human; C497761:NOTCH1 protein, human; C494360:EP300 protein, human; C110550:HDAC1 protein, human; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde