OP14 - Influence of curcumin on a pediatric hepatocellular carcinoma model in vitro and in vivo: significant reduction of alpha-fetoprotein and curcuminoid levels in mice

In children with hepatocellular carcinoma (pHCC) overall survival is poor. In adult HCC several antitumor properties are described in in vitro models for the use of curcumin (CUR). Hepatoma cell lines (HuH6, HepT1, HepG2, HC-AFW1) were treated with CUR or, and Cisplatin (PDDT), cultures were either kept in the dark or exposed to blue light (PDT; 480 nm, 300W, 10 seconds), MTT-tests were performed. ROS production was measured. Reduction of cancer stem cells (CSC) was investigated with FACS analyses. Orthotopic growth of the pediatric hepatocellular carcinoma cell line HC-AWF1 in NSG mice was induced. By the increase serum alpha fetoprotein AFP >5 U/mL mice were treated with micellar CUR, PDDT, or CUR PDDT and compared to controls. Curcuminoid levels in serum and organ lysates as well as AFP serum levels were investigated. In all cell lines IC50 were significantly lower after blue light exposure than after CUR alone (p < 0.001). Blue light exposure resulted in significant ROS production in all cell lines. CUR alone reduced HEK-6D6 positive CSC not as effectively as CDDP alone or as curcumin with PDT. Serum CUR decreased from 3513.89 ± 2791.84 nmol/L two hours after administration to 769.74 ± 448.61 nmol/L after five hours. CUR concentrations significantly differed between organs (p=0.000), highest concentrations were observed in the lungs 11.33 ± 9.17 nmol/Kg, lowest in the brain 0.16 ± 0.24 nmol/Kg. The concentrations in the tumor tissue (2.57 ± 1.49 nmol/Kg) were higher than in the liver (1.77 ± 1.50 nmol/Kg). Combination therapy significantly reduced AFP concentrations compared to control group (week 3: 1.04 ± 0.67 vs. 2.73 ± 0.64, p = 0.004; week 4: 2.05 ± 1.01 vs. 3.35 ± 0.43, respectively, p = 0.02). These data prove the potential of micellar curcumin as a complementary agent in pediatric oncology to enhance the overall survival of patients with pediatric liver tumors.