Liposome-encapsulated curcumin suppresses growth of head and neck squamous cell carcinoma in vitro and in xenografts through the inhibition of nuclear factor kappaB by an AKT-independent pathway.
OBJECTIVE
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.


METHODS
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 kappaB (NFkappaB) activation. Western blot analysis was done to determine the effect of curcumin on the expression of NFkappaB, phospho-IkappaBalpha, 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 NFkappaB 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 NFkappaB 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 NFkappaB 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 NFkappaB 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.
Wang
Dorothy
D
Department of Surgery, VA Greater Los Angeles Healthcare System, and Division of Head and Neck Surgery, David Geffen School of Medicine at University of California-Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Veena
Mysore S
MS
Stevenson
Kerry
K
Tang
Christopher
C
Ho
Baran
B
Suh
Jeffrey D
JD
Duarte
Victor M
VM
Faull
Kym F
KF
Mehta
Kapil
K
Srivatsan
Eri S
ES
Wang
Marilene B
MB
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D003474:Curcumin / Q000008:administration & dosage* / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009368:Neoplasm Transplantation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D000970:Antineoplastic Agents; D008081:Liposomes; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin