Liposome-encapsulated curcumin

In vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis

Authors

  • Lan Li M.D.,

    1. Division of Cancer Medicine, Phase I Program and Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Fadi S. Braiteh M.D.,

    1. Division of Cancer Medicine, Phase I Program and Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Razelle Kurzrock M.D.

    Corresponding author
    1. Division of Cancer Medicine, Phase I Program and Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    • FACP-Unit 422, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, P.O. Box 301402, Houston, TX 77230-1402
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    • Fax: (713) 745-2374


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.

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