Suberoylanilide hydroxamic acid limits migration and invasion of glioma cells in two and three dimensional culture.
High grade gliomas are aggressive cancers that are not well addressed by current chemotherapies, in large measure because these drugs do not curtail the diffuse invasion of glioma cells into brain tissue surrounding the tumor. Here, we investigate the effects of suberoylanilide hydroxamic acid (SAHA) on glioma cells in 2D and 3D in vitro assays, as SAHA has previously been shown to significantly increase apoptosis, decrease proliferation, and interfere with migration in other cell lines. We find that SAHA has significant independent effects on proliferation, migration, and invasion. These effects are seen in both 2D and 3D culture. In 3D culture, with glioma spheroids embedded in collagen I matrices, SAHA independently limits both glioma invasion and the reorganization of the tumor surroundings that usually proceeds such invasion. The decreased matrix reorganization and invasion is not accompanied by decreased production or activity of matrix-metalloproteases but instead may be related to increased cell-cell adhesion.
An
Zhihua
Z
Department of Chemistry, Columbia University, New York, NY 10027, United States.
Gluck
Christian B
CB
Choy
Megan L
ML
Kaufman
Laura J
LJ
D016475:3T3 Cells; D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D000077337:Vorinostat
D006877:Hydroxamic Acids; D000077337:Vorinostat