PMID- 16755000
OWN - NLM
STAT- MEDLINE
DCOM- 20100212
LR  - 20231213
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 29
IP  - 6
DP  - 2006 Jun
TI  - Silibinin prevents UV-induced HaCaT cell apoptosis partly through inhibition of 
      caspase-8 pathway.
PG  - 1096-101
AB  - Silymarin is a polyphenolic flavonoid from milk thistle (Silybum marianum), which 
      has anti-inflammatory, cytoprotective, and anticarcinogenic effects. In this 
      study, we assessed the effect of silibinin (Fig. 1), the major active compound in 
      silymarin, on ultraviolet light (UV)-induced cell apoptosis in HaCaT cells, a 
      human keratinocyte cell line. Pretreatment with silibinin 500 microM 
      significantly inhibited UV-induced apoptosis in HaCaT cells after 9 h incubation. 
      The expression of Fas-associating protein with death domain (FADD), a downstream 
      molecule of the death receptor pathway, was completely eliminated by silibinin 
      treatment in UV-irradiated HaCaT cells, followed by inhibition of cleavage of 
      procaspase-8, whose activation induced cell apoptosis and decreased the release 
      of cytochrome c from mitochondria. The caspase-8 inhibitor z-IETD-fmk at 10 
      microM increased the ratio of UV-irradiated HaCaT cell viability, suggesting that 
      UV-induced HaCaT cell apoptosis was partially due to activation of the caspase-8 
      pathway. Moreover, UV-induced cleavage of procaspase-3 and digestion of its 
      substrates, the inhibitor of caspase-activated DNase (ICAD) and poly-(ADP-ribose) 
      polymerase (PARP), were also reduced by silibinin pretreatment. While 
      unexpectedly, it was found in our study that pretreatment with silibinin 
      increased HaCaT cell death by CD95 agonistic antibody CH11. Consequently, the 
      protective effect of silibinin against UV irradiation in HaCaT cells is exerted 
      by inactivation of caspase-8 after direct down-regulation of FADD expression, 
      resulting in blockage of UV-induced apoptosis.
FAU - Li, Lin-Hao
AU  - Li LH
AD  - China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang 
      Pharmaceutical University, Shenyang, China.
FAU - Wu, Li-Jun
AU  - Wu LJ
FAU - Tashiro, Shin-ichi
AU  - Tashiro S
FAU - Onodera, Satoshi
AU  - Onodera S
FAU - Uchiumi, Fumiaki
AU  - Uchiumi F
FAU - Ikejima, Takashi
AU  - Ikejima T
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Caspase Inhibitors)
RN  - 0 (FADD protein, human)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Silymarin)
RN  - 0 (fas Receptor)
RN  - 4RKY41TBTF (Silybin)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Apoptosis/*drug effects/radiation effects
MH  - Blotting, Western
MH  - Caspase 8
MH  - *Caspase Inhibitors
MH  - Cell Culture Techniques
MH  - Cell Line
MH  - Cell Survival/drug effects/radiation effects
MH  - Cytochromes c/metabolism
MH  - DNA Fragmentation/*drug effects/radiation effects
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Fas-Associated Death Domain Protein/metabolism
MH  - Humans
MH  - Keratinocytes/*drug effects/radiation effects
MH  - Silybum marianum/chemistry
MH  - Molecular Structure
MH  - Signal Transduction/drug effects/radiation effects
MH  - Silybin
MH  - Silymarin/isolation & purification/pharmacology
MH  - *Ultraviolet Rays
MH  - fas Receptor/biosynthesis
EDAT- 2006/06/07 09:00
MHDA- 2010/02/13 06:00
CRDT- 2006/06/07 09:00
PHST- 2006/06/07 09:00 [pubmed]
PHST- 2010/02/13 06:00 [medline]
PHST- 2006/06/07 09:00 [entrez]
AID - JST.JSTAGE/bpb/29.1096 [pii]
AID - 10.1248/bpb.29.1096 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2006 Jun;29(6):1096-101. doi: 10.1248/bpb.29.1096.