Pommepuy I, Terro F, Petit B, Trimoreau F, Bellet V, Robert S,
Hugon J, Labrousse F, Yardin C.Brefeldin A induces
apoptosis and cell cycle blockade in glioblastoma cell lines.
Oncology. 2003;64(4):459-67.
Department of Pathology, Limoges University Hospital, Faculty of
Medicine, Limoges, France.
Brefeldin A , a fungal metabolite known to affect the structure
and function of the Golgi apparatus, has recently been shown to
induce apoptosis and cell growth inhibition in various human
cell lines. Glioblastomas (GB) are cerebral tumors with poor
prognosis, which display resistance to current therapies
including radio- and chemotherapy. The objective of this study
was to investigate Brefeldin A effects in three human GB
cell lines (SA4, SA146 and U87MG cells). Compared with control
cells, about 60% of cell growth inhibition was observed in
Brefeldin A (100 ng/ml for 24 h)-exposed cells in the
three cell lines. Furthermore, in SA4 and SA146 cells, Brefeldin
A was able to induce a time- and dose-dependent apoptosis
detected by DAPI staining, TUNEL assay and flow-cytometric
analysis. Since p53 expression was not modified after Brefeldin
A exposure, Brefeldin A -induced apoptosis may follow a
p53-independent pathway, as already reported. In the same way,
Brefeldin A did not alter Bcl-2, Bax and Mcl-1 expression.
Cell cycle analysis revealed a cell cycle arrest in early G0/G1
phase with an increase in G0/G1 cell population (70% in control
cells vs. 83% in exposed cells) associated with a decrease in
the S cell population (14% in control cells vs. 5.5% in exposed
cells). The Ki67 labeling index also confirmed the cell cycle
blockade. Our results suggest that Brefeldin A may be a
potent cell cycle modulator and inducer of apoptosis in GB cell
lines, and therefore may become a promising candidate for the
chemotherapeutic treatment of gliomas. Copyright 2003 S. Karger
AG, Basel
PMID: 12759546 |
