title: Silibinin inhibits tumor growth in a murine orthotopic hepatocarcinoma model and activates the TRAIL apoptotic signaling pathway.
abstract: OBJECTIVE
  The present study investigated the molecular mechanism of silibinin-induced antitumoral effects in hepatocarcinoma Hep-55.1C cells in vitro and in a hepatocarcinoma model in mice.
  
  
  METHODS
  Cell death was analyzed by flow cytometry. The genetic expression of apoptotic and inflammatory biomarkers was assessed by quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). Orthotopic grafting of Hep-55.1C cells into the liver of C57BL/6J mice was performed, and tumor growth was followed by micro-computed imaging.
  
  
  RESULTS
  Silibinin activated the extrinsic apoptotic pathway in Hep55.1C cells, as attested by the up-regulation of TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL Death receptor 5 (DR5) transcripts, and by the activation of caspase-3 and -8. After grafting of Hep-55.1C cells into mouse liver, the oral administration of silibinin at 700 mg/kg body weight for four weeks caused a significant reduction of tumor growth, associated with the down-regulation of inflammatory components [matrix metalloproteinase -7 and -9, (MMP-7, MMP-9), Interleukin-1 beta (IL1β)], the up-regulation of apoptotic mediators (TRAIL, DR5), and caspase-3 activation.
  
  
  CONCLUSIONS
  Silibinin treatment exerted important anticarcinogenic effects, including the activation of TRAIL death receptor apoptotic signaling pathway in Hep-55.1C hepatocarcinoma cells, both in vitro and in hepatocarcinoma grafts in mice.
authors: Laboratory of Nutritional Cancer Prevention, IRCAD, 1, Place de l'hôpital, 67091 Strasbourg-Cedex, France.
authors: Souad
authors: S
authors: Bousserouel
authors: Gaetan
authors: G
authors: Bour
authors: Henriette
authors: H
authors: Kauntz
authors: Francine
authors: F
authors: Gossé
authors: Jacques
authors: J
authors: Marescaux
authors: Francis
authors: F
authors: Raul
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D012838:Silymarin; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D000077385:Silybin