Reference : NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminol...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy.
Coupienne, Isabelle mailto [Université de Liège - ULiège > > GIGA-R : Virologie - Immunologie >]
Bontems, Sébastien mailto [Centre Hospitalier Universitaire de Liège - CHU > > Hématologie biologique et immuno hématologie >]
Dewaele, M. [> > > >]
Rubio, N. [> > > >]
Habraken, Yvette mailto [Université de Liège - ULiège > > GIGA-R : Virologie - Immunologie >]
Fulda, S. [> > > >]
Agostinis, P. [> > > >]
Piette, Jacques mailto [Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie - Département des sciences de la vie - GIGA-Research >]
Biochemical Pharmacology
Elsevier Science
Yes (verified by ORBi)
United Kingdom
[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.
Copyright A(c) 2010. Published by Elsevier Inc.

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