gms | German Medical Science

Introduction: Malignant hepatoblastoma ist the most common liver tumor in children. Nowadays with operative treatment and perioperative chemotherapy about 75% of the patients survive the first 5 years after diagnosis. Nevertheless there are still tumors which are resistant to common therapy. Particularly in the early postoperative phase when the infantile body is stressed from operation it seems to be expedient to use adjuvant treatment which doesn't debilitate the infantile body additionally. The natural occurring antioxidant agent epigallocatechin-3-gallate (EGCG), a flavonoid which represents one third of the dry mass of green tea, seems to be a potential agent for induction of apoptosis.

Materials and methods: Initially the effects of ECGC on growth performance (MTT-assays) and apoptosis induction (caspase-3 immunofluorescence) of hepatoblastoma cell lines HUH6, HepT1, HepT3 and HepG2 were examined. Then we analysed hepatoblastoma associated genes via real-time PCR. Oral application of EGCG was performed exclusively and in addition to chemotherapy (cisplatin) in a following animal model (xenografttumors in nude mice).

Results: In vitro a nearly total reduction of tumor cell vitality after EGCG substitution in comparison to cells of the fibroblast culture was shown. Additionally a significant induction of apoptosis could be demonstrated morphologically and via immunofluorescence. EGCG repressed the expression of important Wnt-signalling pathway genes (c-myc and cyclin D1) and led to a re-expression of epigenetically repressed genes (HHIP, SFRP1 and IGFBP3). First results could be confirmed via animal experiments.

Conclusion: Preclinical investigation of epigallocatechin-3-gallate showed promising findings concerning apoptosis induction, inhibition of Wnt-signaling pathway and re-expression of epigenetically repressed genes. For this reason EGCG could be an appropriate supplementation of the treatment plan of hepatoblastoma. Studies about possible pharmaceutical form and dosage have to be performed in the future.