Effect of curcumin on nuclear factor kappaB signaling pathways in human chronic myelogenous K562 leukemia cells.
Curcumin, a natural product isolated from the plant Curcuma longa, has a diverse range of molecular targets that influence numerous biochemical and molecular cascades. Curcumin has been shown to inhibit nuclear factor kappaB (NF-kappaB) activation at several steps in the NF-kappaB signaling pathways and thereby controls numerous NF-kappaB-regulated genes involved in various diseases. In the present study, we investigated the effect of curcumin pretreatment on 84 tumor necrosis factor-alpha (TNF-alpha)-activated genes of NF-kappaB pathways in K562 cells, using a real-time PCR array. Our results show that transcription of 29 NF-kappaB-related mRNAs was significantly downregulated (CARD4, CCL2, CD40, CSF2, F2R, ICAM1, IKBKB, IKBKE, IL1A, IL1B, IL6, IL8, IRAK2, MALT1, MAP3K1, MYD88, NFKB1, NFKB2, NFKBIA, PPM1A, RAF1, RELB, STAT1, TLR3, TNF, TNFalphaIP3, TNFSF10, and TICAM1), whereas 10 mRNAs were induced (AGT, CASP1, CSF3, FOS, IFNG, IL10, TICAM2, TLR2, TLR9, and TNFRSF7). Western blot analysis of CD40, NFKB1 (p50), RELB, NFKBIA (IkappaBalpha), and IL10 as well as an IL8 secretion assay confirmed our results. Taken together, we show that curcumin regulates an impressive number of NF-kappaB genes within the different NF-kappaB signaling pathways.
Reuter
Simone
S
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, Luxembourg, Luxembourg. simone.reuter@lbmcc.lu
Charlet
Jessica
J
Juncker
Tom
T
Teiten
Marie-Hélène
MH
Dicato
Mario
M
Diederich
Marc
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D019013:CD40 Antigens / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D051841:Transcription Factor RelB / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D019013:CD40 Antigens; D016209:Interleukin-8; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C497593:RELB protein, human; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D051841:Transcription Factor RelB; D003474:Curcumin