Document Detail


Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis.
MedLine Citation:
PMID:  16092118     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Because a role for nuclear factor-kappaB (NF-kappaB) has been implicated in the pathogenesis of pancreatic carcinoma, this transcription factor is a potential target for the treatment of this devastating disease. Curcumin (diferuloylmethane) is a phytochemical with potent NF-kappaB-inhibitory activity. It is pharmacologically safe, but its bioavailability is poor after oral administration. METHODS: The authors encapsulated curcumin in a liposomal delivery system that would allow intravenous administration. They studied the in vitro and in vivo effects of this compound on proliferation, apoptosis, signaling, and angiogenesis using human pancreatic carcinoma cells. NF-kappaB was constitutively active in all human pancreatic carcinoma cell lines evaluated and liposomal curcumin consistently suppressed NF-kappaB binding (electrophoretic mobility gel shift assay) and decreased the expression of NF-kappaB-regulated gene products, including cyclooxygenase-2 (immunoblots) and interleukin-8 (enzyme-linked immunoassay), both of which have been implicated in tumor growth/invasiveness. These in vitro changes were associated with concentration and time-dependent antiproliferative activity (3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide assay [MTT assay]) and proapoptotic effects (annexin V/propidium iodide staining [fluorescence-activated cell sorting] and polyadenosine-5'-diphosphate-ribose-polymerase cleavage). RESULTS: The activity of liposomal curcumin was equal to or better than that of free curcumin at equimolar concentrations. In vivo, curcumin suppressed pancreatic carcinoma growth in murine xenograft models and inhibited tumor angiogenesis. CONCLUSIONS: Liposomal curcumin down-regulated the NF-kappaB machinery, suppressed growth, and induced apoptosis of human pancreatic cells in vitro. Antitumor and antiangiogenesis effects were observed in vivo. The experiments in the current study provide a biologic rationale for treatment of patients suffering from pancreatic carcinoma with this nontoxic phytochemical encapsulated in liposomes for systemic delivery.
Authors:
Lan Li; Fadi S Braiteh; Razelle Kurzrock
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer     Volume:  104     ISSN:  0008-543X     ISO Abbreviation:  Cancer     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-06     Completed Date:  2005-10-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1322-31     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2005 American Cancer Society.
Affiliation:
Division of Cancer Medicine, Phase I Program and Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, 77230, USA.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / pharmacology*
Animals
Apoptosis / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects
Curcumin / administration & dosage*
Cyclooxygenase 2
Female
Humans
Liposomes
Membrane Proteins
Mice
NF-kappa B / antagonists & inhibitors
Neovascularization, Pathologic / prevention & control*
Pancreatic Neoplasms / drug therapy*,  pathology
Prostaglandin-Endoperoxide Synthases / drug effects
Grant Support
ID/Acronym/Agency:
1 P20 CA101936-01/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Liposomes; 0/Membrane Proteins; 0/NF-kappa B; 458-37-7/Curcumin; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases

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