Document Detail


Preclinical assessment of curcumin as a potential therapy for B-CLL.
MedLine Citation:
PMID:  16947318     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Curcumin, the principle component of the spice turmeric, has been used as an anti-inflammatory medication in India and China for centuries. Recent studies, predominantly using actively dividing cell lines, have suggested that this compound could be used as a chemopreventative or therapeutic agent for epithelial tumors. As curcumin has been reported to inhibit the NIK/IKK complex, an activity that would be expected to induce apoptosis in B cell malignancies, we sought to determine whether curcumin induces apoptosis in vitro in primary chronic lymphocytic leukemia (B-CLL) cells. Primary leukemic cells were incubated with varying dosages of curcumin, followed by assessment for apoptosis. The role of PPARgamma or NF-kappaB signaling in curcumin-induced apoptosis was examined by cotreatment with a PPARgamma antagonist or EMSA of nuclear NFkappaB complexes. We also examined whether a clinically achievable concentration of curcumin (1 microM) would augment the apoptotic effects of fludarabine, dexamethasone, vincristine or the PDE4 inhibitor rolipram. In B-CLL cells from 14 patients, curcumin-induced apoptosis with a mean EC(50) of 5.5 microM. In contrast, the EC(50) for whole mononuclear cells from a healthy donor was 21.8 microM. In a 48 hr wash-out time course, curcumin-induced apoptosis was time-dependent, with a substantial reduction in apoptosis observed when curcumin was removed after 5 hr. Curcumin treatment reduced basal nuclear NF-kappaB levels and 1 microM curcumin augmented both vinca alkaloid and PDE4 inhibitor-induced apoptosis in B-CLL cells. Our studies suggest that curcumin may augment the efficacy of established or experimental therapies for B-CLL.
Authors:
Peter C Everett; John A Meyers; Anthony Makkinje; Mohammed Rabbi; Adam Lerner
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  American journal of hematology     Volume:  82     ISSN:  0361-8609     ISO Abbreviation:  Am. J. Hematol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-12     Completed Date:  2007-02-21     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  7610369     Medline TA:  Am J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  23-30     Citation Subset:  IM    
Affiliation:
Section of Hematology and Oncology, Evans Department of Medicine, Boston Medical Center, Boston, Massachusetts 02118, USA.
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MeSH Terms
Descriptor/Qualifier:
3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors,  metabolism
Antineoplastic Agents / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / pharmacology
Apoptosis / drug effects*
Curcumin / pharmacology*
Cyclic Nucleotide Phosphodiesterases, Type 4
Dexamethasone / pharmacology
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Female
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*,  metabolism
Male
NF-kappa B / metabolism
PPAR gamma / metabolism
Protein-Serine-Threonine Kinases / antagonists & inhibitors,  metabolism
Rolipram / pharmacology
Signal Transduction / drug effects*
Tumor Cells, Cultured
Vidarabine / analogs & derivatives,  pharmacology
Vincristine / pharmacology
Grant Support
ID/Acronym/Agency:
CA 106705/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/NF-kappa B; 0/PPAR gamma; 21679-14-1/fludarabine; 458-37-7/Curcumin; 50-02-2/Dexamethasone; 5536-17-4/Vidarabine; 57-22-7/Vincristine; 61413-54-5/Rolipram; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.25/NF-kappa B kinase; EC 3.1.4.17/3',5'-Cyclic-AMP Phosphodiesterases; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 4

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