title: BH3 mimetics reduce adhesion and migration of hepatoblastoma and hepatocellular carcinoma cells.
abstract: Advanced stages of tumour and development of metastases are the two major problems in treating liver tumours such as hepatoblastoma (HB) and hepatocellular carcinoma (HCC), in paediatric patients. Modulation of apoptosis in HB cells enhances the sensitivity of these cells towards various drugs and has been discussed to enforce treatment. We analysed the effect of apoptosis modulators, BH3 mimetics, on mechanisms of dissemination such as adhesion or migration of HB and HCC cells. BH3 mimetics such as ABT-737 and obatoclax can reduce cell migration in a scratch assay as well as adhesion of HB and HCC cells to matrigel. Immunofluorescence staining of F-actin demonstrated that development of lamellipodia, which are important for migration, decreased. BH3 mimetics increase the level of activated caspases 3 and 7 in HUH6 cells. This results in the degradation of GTPase Cdc42, which can be determined by western blot analysis. A pan-caspase inhibitor can block the migration and degradation of Rho-GTPase. In summary, our study showed that BH3 mimetics not only enhance drug sensitivity but also may prevent metastasis by inhibiting HB and HCC cell motility.
authors: Department of Pediatric Surgery and Urology, University Children's Hospital, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany.
authors: Fabian
authors: F
authors: Vogt
authors: Justus
authors: J
authors: Lieber
authors: Alexander
authors: A
authors: Dewerth
authors: Alexander
authors: A
authors: Hoh
authors: Jörg
authors: J
authors: Fuchs
authors: Sorin
authors: S
authors: Armeanu-Ebinger
mesh_terms: D000199:Actins / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D018197:Hepatoblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007211:Indoles; D009362:Neoplasm Metastasis; D009596:Nitrophenols / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D059748:Proteolysis; D011554:Pseudopodia / Q000737:chemistry; D011758:Pyrroles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: C501332:ABT-737; D000199:Actins; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D061945:Caspase Inhibitors; D007211:Indoles; D009596:Nitrophenols; D009842:Oligopeptides; D010879:Piperazines; D011758:Pyrroles; D013449:Sulfonamides; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020764:cdc42 GTP-Binding Protein; C520962:obatoclax