PMID- 18709644
OWN - NLM
STAT- MEDLINE
DCOM- 20080916
LR  - 20211203
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 123
IP  - 9
DP  - 2008 Nov 1
TI  - Ebselen sensitizes glioblastoma cells to Tumor Necrosis Factor (TNFalpha)-induced 
      apoptosis through two distinct pathways involving NF-kappaB downregulation and 
      Fas-mediated formation of death inducing signaling complex.
PG  - 2204-12
LID - 10.1002/ijc.23771 [doi]
AB  - Resistance to tumor necrosis factor (TNFalpha)-induced apoptosis in various 
      cancer cells has been attributed to the activation of the transcription factor 
      NF-kappaB. Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]one)-a selenoorganic 
      compound is known to prevent TNFalpha-mediated NF-kappaB activity. As 
      glioblastoma are resistant to the cytotoxic effect of TNFalpha, we investigated 
      the potential of Ebselen in sensitizing glioma cells to TNFalpha-induced 
      apoptosis. Although treatment with Ebselen reduced viability of glioma cells, 
      cotreatment with TNFalpha enhanced apoptosis further through alteration of 
      TNFalpha-mediated signaling pathways. Sensitization of TNFalpha activated glioma 
      cells to apoptosis by Ebselen involved 2 pathways: (i) abrogation of TNFalpha 
      induced NF-kappaB activation and (ii) induction of Fas-associated death inducing 
      signaling complex (DISC) formation. Ebselen inhibited the prosurvival pathway 
      mediated by NF-kappaB by altering the association of TNF receptor associated 
      factor 2 (TRAF2) with TNFalpha receptor associated death domain (TRADD) in the 
      TNFR1-TRADD-TRAF2 complex -an interaction crucial for mediating NF-kappaB 
      activity. Ebselen also induced the formation of DISC involving Fas, 
      Fas-associated death domain (FADD) and active caspase 8 to transduce apoptotic 
      signals in situations where NF-kappaB function was inhibited. Cotreatment with 
      Ebselen and TNFalpha induced G2/M phase arrest in cell cycle and modulated the 
      expression of molecules involved in cell cycle progression. These results raise 
      the possibility of overcoming resistance to TNFalpha-induced apoptosis by 
      cotreatment with organoselenium Ebselen as a strategy to kill glioma cells.
CI  - (c) 2008 Wiley-Liss, Inc.
FAU - Sharma, Vivek
AU  - Sharma V
AD  - National Brain Research Centre, Manesar, Haryana, India.
FAU - Tewari, Richa
AU  - Tewari R
FAU - Sk, Ugir Hossain
AU  - Sk UH
FAU - Joseph, Christy
AU  - Joseph C
FAU - Sen, Ellora
AU  - Sen E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Azoles)
RN  - 0 (FADD protein, human)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Isoindoles)
RN  - 0 (NF-kappa B)
RN  - 0 (Organoselenium Compounds)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (TNF Receptor-Associated Death Domain Protein)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
RN  - 40X2P7DPGH (ebselen)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Azoles/*pharmacology
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Down-Regulation
MH  - Fas-Associated Death Domain Protein/metabolism
MH  - Glioblastoma/*drug therapy/metabolism/pathology
MH  - Humans
MH  - Isoindoles
MH  - NF-kappa B/*antagonists & inhibitors/genetics
MH  - Organoselenium Compounds/*pharmacology
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Signal Transduction
MH  - TNF Receptor-Associated Death Domain Protein/metabolism
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - fas Receptor/*physiology
EDAT- 2008/08/19 09:00
MHDA- 2008/09/17 09:00
CRDT- 2008/08/19 09:00
PHST- 2008/08/19 09:00 [pubmed]
PHST- 2008/09/17 09:00 [medline]
PHST- 2008/08/19 09:00 [entrez]
AID - 10.1002/ijc.23771 [doi]
PST - ppublish
SO  - Int J Cancer. 2008 Nov 1;123(9):2204-12. doi: 10.1002/ijc.23771.