PMID- 22753701
OWN - NLM
STAT- MEDLINE
DCOM- 20121008
LR  - 20181201
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 32
IP  - 7
DP  - 2012 Jul
TI  - Silibinin inhibits tumor growth in a murine orthotopic hepatocarcinoma model and 
      activates the TRAIL apoptotic signaling pathway.
PG  - 2455-62
AB  - AIM: 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. MATERIALS AND 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 (IL1beta)], the up-regulation of apoptotic mediators (TRAIL, 
      DR5), and caspase-3 activation. CONCLUSION: 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.
FAU - Bousserouel, Souad
AU  - Bousserouel S
AD  - Laboratory of Nutritional Cancer Prevention, IRCAD, 1, Place de l'hopital, 67091 
      Strasbourg-Cedex, France.
FAU - Bour, Gaetan
AU  - Bour G
FAU - Kauntz, Henriette
AU  - Kauntz H
FAU - Gosse, Francine
AU  - Gosse F
FAU - Marescaux, Jacques
AU  - Marescaux J
FAU - Raul, Francis
AU  - Raul F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Silymarin)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Tnfsf10 protein, mouse)
RN  - 4RKY41TBTF (Silybin)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cell Growth Processes/drug effects
MH  - Cell Line, Tumor
MH  - Disease Models, Animal
MH  - Gene Expression Regulation, Neoplastic
MH  - Liver Neoplasms, Experimental/*drug therapy/genetics/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/biosynthesis/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Silybin
MH  - Silymarin/*pharmacology
MH  - TNF-Related Apoptosis-Inducing Ligand/biosynthesis/genetics/*metabolism
EDAT- 2012/07/04 06:00
MHDA- 2012/10/09 06:00
CRDT- 2012/07/04 06:00
PHST- 2012/07/04 06:00 [entrez]
PHST- 2012/07/04 06:00 [pubmed]
PHST- 2012/10/09 06:00 [medline]
AID - 32/7/2455 [pii]
PST - ppublish
SO  - Anticancer Res. 2012 Jul;32(7):2455-62.