title: 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.
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.
authors.affiliation: Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Bortel
authors.affiliation: Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Sorin
authors.initials: S
authors.lastname: Armeanu-Ebinger
authors.affiliation: Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Evi
authors.initials: E
authors.lastname: Schmid
authors.affiliation: Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Kirchner
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Division of Biofunctionality and Safety of Food, D-70599 Stuttgart, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Frank
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Division of Biofunctionality and Safety of Food, D-70599 Stuttgart, Germany.
authors.forename: Alexa
authors.initials: A
authors.lastname: Kocher
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Division of Biofunctionality and Safety of Food, D-70599 Stuttgart, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Schiborr
authors.affiliation: Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Steven
authors.initials: S
authors.lastname: Warmann
authors.affiliation: Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Fuchs
authors.affiliation: Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Ellerkamp
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects*; D002648:Child; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; D051176:beta Catenin; D003474:Curcumin
keywords: cisplatin; curcumin; hepatocellular carcinoma; orthotopic tumor model; pediatric