Article (Scientific journals)
NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy.
Coupienne, Isabelle; Bontems, Sébastien; Dewaele, M. et al.
2011In Biochemical Pharmacology
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Abstract :
[en] Glioblastoma constitute the most frequent and deadliest brain tumors of astrocytic origin. They are very resistant to all current therapies and are associated with a huge rate of recurrence. In most cases, this type of tumor is characterized by a constitutive activation of the nuclear factor-kappaB (NF-kappaB). This factor is known to be a key regulator of various physiological processes such as inflammation, immune response, cell growth or apoptosis. In the present study, we explored the role of NF-kappaB activation in the sensitivity of human glioblastoma cells to a treatment by 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT). 5-ALA is a physiological compound widely used in PDT as well as in tumor photodetection (PDD). Our results show that inhibition of NF-kappaB improves glioblastoma cell death in response to 5-ALA-PDT. We then studied the molecular mechanisms underlying the cell death induced by PDT combined or not with NF-kappaB inhibition. We found that apoptosis was induced by PDT but in an incomplete manner and that, unexpectedly, NF-kappaB inhibition reduced its level. Oppositely PDT mainly induces necrosis in glioblastoma cells and NF-kappaB is found to have anti-necrotic functions in this context. The autophagic flux was also enhanced as a result of 5-ALA-PDT and we demonstrate that stimulation of autophagy acts as a pro-survival mechanism confering protection against PDT-mediated necrosis. These data point out that 5-ALA-PDT has an interesting potential as a mean to treat glioblastoma and that inhibition of NF-kappaB renders glioblastoma cells more sensitive to the treatment.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Coupienne, Isabelle ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Bontems, Sébastien ;  Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Dewaele, M.
Rubio, N.
Habraken, Yvette ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Fulda, S.
Agostinis, P.
Piette, Jacques ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie - Département des sciences de la vie - GIGA-Research
Language :
English
Title :
NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy.
Publication date :
March 2011
Journal title :
Biochemical Pharmacology
ISSN :
0006-2952
eISSN :
1873-2968
Publisher :
Elsevier Science, Oxford, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright A(c) 2010. Published by Elsevier Inc.
Available on ORBi :
since 18 January 2011

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