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.

Nicola Bortel,Jörg Fuchs,Verena Ellerkamp,Jan Frank,Evi Schmid,Alexa Kocher,Bettina Kirchner,Steven Warmann,Christina Schiborr,Sorin Armeanu-Ebinger

doi:10.18632/oncotarget.5673

Nicola Bortel, Jörg Fuchs + Show 8 more

Open Access

https://doi.org/10.18632/oncotarget.5673

Copy DOI

Journal: Oncotarget	Publication Date: Oct 19, 2015
Citations: 32	License type: cc-by

Affiliation: University of Tübingen, University of Hohenheim

Abstract

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.

Highlights

Malignant liver tumors in childhood are rare, the annual incidence rate for the United States was stated with 1.8 cases per million children younger than 15 years [1]
We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines
Micellar curcumin in combination with cisplatin can be a promising strategy for treatment of pediatric HCC

Summary

Introduction

Malignant liver tumors in childhood are rare, the annual incidence rate for the United States was stated with 1.8 cases per million children younger than 15 years [1]. While hepatoblastomas (HB) account for the majority (91%) of these tumors, pediatric hepatocellular carcinoma (pHCC) accounts for approximately 1%. The outcome in hepatoblastoma has improved during the last decades, but still the patients with PRETEXT 4 stages suffer from poor 5-year-survival rates of 20–30% [2, 3]. The most cases of pediatric HCC present in advanced stages with poor outcome and 5-year overall survival rates of only 10–23% [1, 4]. Curcumin inhibits diethylnitrosamine induced hepatocellular carcinoma in rats, and leads to apoptosis of HCC cells in vitro [9, 10]

Methods

Results

Conclusion