INHIBITOR OF APOPTOSIS PROTEINS DETERMINE GLIOBLASTOMAS STEMLIKE CELLS FATE IN AN OXYGENDEPENDENT MANNER

INHIBITOR OF APOPTOSIS PROTEINS DETERMINE GLIOBLASTOMAS STEMLIKE CELLS FATE IN AN OXYGENDEPENDENT MANNER

11^th International Conference on Cancer Stem Cells and Oncology Research
June 11-13, 2018 | Dublin, Ireland

Aurelie Tchoghandjian

Axe Marseille Université, France

Scientific Tracks Abstracts : J Med Oncl Ther

Abstract:

Smac mimetics (SMs) are inhibitor of apoptosis proteins (IAPs) antagonists. In glioblastomas (GBs), SMs can trigger apoptotic and non-apoptotic processes1, 2, 3. As GBs are highly hypoxic, we investigated SM GDC-0152 effect in GB stem-like cells according to oxygen level. We showed that in an environment rich in oxygen (normoxia), GDC-0152 induced loss of stem-cell properties. Unexpectedly, in an environment deprived of oxygen (hypoxia), it triggered apoptosis and decreased cell proliferation. Analysis of Serine-Threonine Kinases activation upon GDC0152 treatment revealed involvement of different signaling pathways according to oxygen level. In normoxia, NF-κB pathway was activated and in hypoxia, GDC-0152 efficacy was ATR- and TNFα-dependent. This work shows that GDC-0152 triggers anti-tumoral effects whatever the tumoral oxygen pressure, therefore SMs appear as promising molecules in GBs treatment.

Biography:

Aurélie Tchoghandjian is currently working in INP – Institut de Neurophysiopathologie, Axe Marseille Université, France Email:aurelie.tchoghandjian@univ-amu.fr

PDF HTML