Document Detail


Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-kappaB and STAT3 pathways in Hodgkin's lymphoma cells.
MedLine Citation:
PMID:  18386790     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although treatment of Hodgkin's lymphoma (HL) with a multi-drug approach has been very successful, its toxicity becomes evident after several years as secondary malignancies and cardiovascular disease. Therefore, the current goal in HL treatment is to find new therapies that specifically target the deregulated signaling cascades, such as NF-kappaB and STAT3, which cause Hodgkin and Reed-Sternberg (H-RS) cell proliferation and resistance of apoptosis. Based on the above information, we investigated the capacity of curcumin to inhibit NF-kappaB and STAT3 in H-RS cells, characterizing the functional consequences. Curcumin is incorporated into H-RS cells and acts inhibiting both NF-kappaB and STAT3 activation, leading to a decreased expression of proteins involved in cell proliferation and apoptosis, e.g. Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1, survivin, c-myc and cyclin D1. Interestingly, curcumin caused cell cycle arrest in G2-M and a significant reduction (80-97%) in H-RS cell viability. Furthermore, curcumin triggered cell death by apoptosis, as evidenced by the activation of caspase-3 and caspase-9, changes in nuclear morphology and phosphatidylserine translocation. The above findings provide a mechanistic rationale for the potential use of curcumin as a therapeutic agent for patients with HL.
Authors:
Gerardo G Mackenzie; Nina Queisser; Manuel L Wolfson; Cesar G Fraga; Ana M Adamo; Patricia I Oteiza
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  123     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-04-30     Completed Date:  2008-06-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  56-65     Citation Subset:  IM    
Copyright Information:
(c) 2008 Wiley-Liss, Inc.
Affiliation:
Department of Nutrition, University of California, Davis, CA 95616, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Blotting, Western
Caspase 3 / metabolism
Caspase 9 / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects*
Curcumin / pharmacology*
Dose-Response Relationship, Drug
Electrophoretic Mobility Shift Assay
Enzyme Activation
Hodgkin Disease / drug therapy*,  metabolism
Humans
NF-kappa B / antagonists & inhibitors*
Phosphatidylserines / genetics
Reed-Sternberg Cells / drug effects,  metabolism*
STAT3 Transcription Factor / antagonists & inhibitors*
Signal Transduction / drug effects
Time Factors
Translocation, Genetic
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/NF-kappa B; 0/Phosphatidylserines; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 458-37-7/Curcumin; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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