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Liposome-Encapsulated Curcumin Suppresses Growth of Head and Neck Squamous Cell Carcinoma In vitro and in Xenografts through the Inhibition of Nuclear Factor B by an AKT-Independent Pathway

Authors' Affiliations: Departments of ¹ Surgery, and ² Pathology, VA Greater Los Angeles Healthcare System, ³ Division of Head and Neck Surgery, David Geffen School of Medicine at University California Los Angeles, ⁴ Department of Psychiatry and Biobehavioral Science, Semel Institute, University of California at Los Angeles, Los Angeles, California; and ⁵ Department of Experimental Therapeutics, M.D. Anderson Cancer Center, University of Texas, Houston, Texas

Requests for reprints: Marilene B. Wang, Division of Head and Neck Surgery, David Geffen School of Medicine at UCLA, CHS 62-132, 10833 Le Conte Avenue, Los Angeles, CA 90095-1624. Phone: 310-268-3407; E-mail: mbwang{at}ucla.edu.

Purpose: The purpose of this study was to determine whether a liposomal formulation of curcumin would suppress the growth of head and neck squamous cell carcinoma (HNSCC) cell lines CAL27 and UM-SCC1 in vitro and in vivo.

Experimental Design: HNSCC cell lines were treated with liposomal curcumin at different doses and assayed for in vitro growth suppression using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A reporter gene assay was done on cell lines to study the effect of liposomal curcumin on nuclear factor B (NFB) activation. Western blot analysis was done to determine the effect of curcumin on the expression of NFB, phospho-IB, phospho-AKT (pAKT), phospho-S6 kinase, cyclin D1, cyclooxygenase-2, matrix metalloproteinase-9, Bcl-2, Bcl-xL, Mcl-1L, and Mcl-1S. Xenograft mouse tumors were grown and treated with intravenous liposomal curcumin. After 5 weeks, tumors were harvested and weighed. Immunohistochemistry and Western blot analyses were used to study the effect of liposomal curcumin on the expression of NFB and pAKT.

Results: The addition of liposomal curcumin resulted in a dose-dependent growth suppression of both cell lines. Liposomal curcumin treatment suppressed the activation of NFB without affecting the expression of pAKT or its downstream target phospho-S6 kinase. Expression of cyclin D1, cyclooxygenase-2, matrix metalloproteinase-9, Bcl-2, Bcl-xL, Mcl-1L, and Mcl-1S were reduced, indicating the effect of curcumin on the NFB pathway. Nude mice xenograft tumors were suppressed after 3.5 weeks of treatment with i.v. liposomal curcumin, and there was no demonstrable toxicity of liposomal curcumin upon autopsy. Immunohistochemistry and Western blot analysis on xenograft tumors showed the inhibition of NFB without affecting the expression of pAKT.

Conclusions: Liposomal curcumin suppresses HNSCC growth in vitro and in vivo. The results suggest that liposomal curcumin is a viable nontoxic therapeutic agent for HNSCC that may work via an AKT-independent pathway.