Liposome-encapsulated curcumin suppresses neuroblastoma growth through nuclear factor-kappa B inhibition

• Published in: Surgery Vol. 151; no. 5; pp. 736 - 744
• Main Authors: ORR, Wayne S, DENBO, Jason W, SAAB, Karim R, MYERS, Adrianne L, NG, Catherine Y, JUNFANG ZHOU, MORTON, Christopher L, PFEFFER, Lawrence M, DAVIDOFF, Andrew M
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 01-05-2012
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Biological and medical sciences; Biomarkers, Tumor - antagonists & inhibitors; Cell Line, Tumor; Cell Proliferation - drug effects; Curcumin - administration & dosage; Curcumin - pharmacology; Curcumin - therapeutic use; Disease Models, Animal; Electrophoretic Mobility Shift Assay; General aspects; Humans; Liposomes; Medical sciences; Mice; Mice, SCID; Neovascularization, Pathologic; Neuroblastoma - drug therapy; Neuroblastoma - metabolism; Neurology; NF-kappa B - antagonists & inhibitors; Real-Time Polymerase Chain Reaction; Treatment Outcome; Tumor Burden - drug effects; Tumors of the nervous system. Phacomatoses; Nervous system diseases; Tyrosine kinase inhibitor; Liposome; Drug carrier; Malignant tumor; Neuroblastoma; Medicine; Polyphenol; Treatment; Surgery; Phenols; Curcumin; Transcription factor NFκB; Inhibition; Autonomic neuropathy; Cancer; Growth factor
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2011.12.014

Nuclear factor-κB (NF-κB) has been implicated in tumor cell proliferation and survival and in tumor angiogenesis. We sought to evaluate the effects of curcumin, an inhibitor of NF-κB, on a xenograft model of disseminated neuroblastoma.
For in vitro studies, neuroblastoma cell lines NB1691, CHLA-20, and SK-N-AS were treated with various doses of liposomal curcumin. Disseminated neuroblastoma was established in vivo by tail vein injection of NB1691-luc cells into SCID mice, which were then treated with 50 mg/kg/day of liposomal curcumin 5 days/week intraperitoneally.
Curcumin suppressed NF-κB activation and proliferation of all neuroblastoma cell lines in vitro. In vivo, curcumin treatment resulted in a significant decrease in disseminated tumor burden. Curcumin-treated tumors had decreased NF-κB activity and an associated significant decrease in tumor cell proliferation and an increase in tumor cell apoptosis, as well as a decrease in tumor vascular endothelial growth factor levels and microvessel density.
Liposomal curcumin suppressed neuroblastoma growth, with treated tumors showing a decrease in NF-κB activity. Our results suggest that liposomal curcumin may be a viable option for the treatment of neuroblastoma that works via inhibiting the NF-κB pathway.