Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoprotein in vitro and in vivo involving the NFkappaB- and the beta-catenin pathways
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Nicola Bortel1, Sorin Armeanu-Ebinger1, Evi Schmid1, Bettina Kirchner1, Jan Frank2, Alexa Kocher2, Christina Schiborr2, Steven Warmann1, Jörg Fuchs1, Verena Ellerkamp1
1Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany
2Institute of Biological Chemistry and Nutrition, University of Hohenheim, Division of Biofunctionality and Safety of Food, D-70599 Stuttgart, Germany
Verena Ellerkamp, e-mail: [email protected]
Keywords: curcumin, hepatocellular carcinoma, cisplatin, pediatric, orthotopic tumor model
Received: April 17, 2015 Accepted: September 13, 2015 Published: October 19, 2015
In children with hepatocellular carcinoma (pHCC) the 5-year overall survival rate is poor. Effects of cytostatic therapies such as cisplatin and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC, several antitumor properties are described for the use of curcumin. Curcumin is one of the best-investigated phytochemicals in complementary oncology without relevant side effects. Its use is limited by low bioavailability. Little is known about the influence of curcumin on pediatric epithelial hepatic malignancies. We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines. As mechanisms of action inhibition of NFkappaB, beta-catenin, and decrease of cyclin D were identified. Using a mouse xenograft model we could show a significant decrease of alpha-fetoprotein after combination therapy of oral micellar curcumin and cisplatin. Significant concentrations of curcuminoids were found in blood samples, organ lysates, and tumor tissue after oral micellar curcumin administration. Micellar curcumin in combination with cisplatin can be a promising strategy for treatment of pediatric HCC.
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