All-trans retinoic acid modulates cancer stem cells of glioblastoma multiforme in an MAPK-dependent manner

Anticancer Res. 2010 Dec;30(12):4915-20.
Karsy M, Albert L, Tobias ME, Murali R, Jhanwar-Uniyal M.
Anticancer Res. 2010 Dec;30(12):4915-20.
Basse dosi di acido all-trans retinoico (ATRA) (10 μM ) possono avere un potenziale terapeutico differenziando il glioblastoma multiforme (GBM) resistente alla terapia con cellule staminali (CSC) e rendendolo sensibile alla terapia mirata.
ATRA/glioblastoma multiforme.

Glioblastoma multiforme (GBM), a grade IV glioma, appears to harbor therapy-resistant cancer stem cells (CSCs) that are the major cause of recurrence. All-trans retinoic acid (ATRA), a derivative of retinoid, is capable of differentiating a variety of stem cells, as well as normal neural progenitor cells, and down-regulates expression of the stem cell marker nestin. This study investigated the effects of ATRA on differentiation, proliferation, self-renewal, and signaling pathways of CSCs in GBM. CSCs differentiated into glial and neuronal lineages at low concentrations of ATRA (10 μM). Proliferation and self renewal of neurospheres were reduced following ATRA, although ATRA induced apopotsis at higher (40 μM) concentrations. Analysis of mitogen-activated protein kinase signaling pathways, specifically extracellular signal-regulated kinases (ERK1/2), showed that ATRA-induced alterations in ERK1/2 were associated with regulation of differentiation, proliferation and apoptosis. These results emphasize that low doses of ATRA may have therapeutic potential by differentiating GBM CSCs and rendering them sensitive 31 to targeted therapy.