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Original Article
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Liposome-encapsulated curcumin
In vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis
Article first published online: 9 AUG 2005
DOI: 10.1002/cncr.21300
Copyright © 2005 American Cancer Society
Additional Information
How to Cite
Li, L., Braiteh, F. S. and Kurzrock, R. (2005), Liposome-encapsulated curcumin. Cancer, 104: 1322–1331. doi: 10.1002/cncr.21300
Publication History
- Issue published online: 31 AUG 2005
- Article first published online: 9 AUG 2005
- Manuscript Accepted: 4 MAY 2005
- Manuscript Revised: 25 MAR 2005
- Manuscript Received: 7 MAR 2005
Funded by
- Morton and Angela Topfer Fund for Pancreatic Cancer Research
- SPORE in Pancreatic Cancer. Grant Number: 1 P20 CA101936-01
- Abstract
- Article
- References
- Cited By
Keywords:
- proliferation;
- apoptosis;
- angiogenesis;
- curcumin
Abstract
BACKGROUND
Because a role for nuclear factor-κB (NF-κB) 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-κB-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-κB was constitutively active in all human pancreatic carcinoma cell lines evaluated and liposomal curcumin consistently suppressed NF-κB binding (electrophoretic mobility gel shift assay) and decreased the expression of NF-κB-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-κB 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. Cancer 2005. © 2005 American Cancer Society.