All-trans retinoic acid influences viability, migration and adhesion of U251 glioblastoma cells

Abstract

Glioblastoma (GBM) is one of the most aggressive and deadly forms of cancer. Literature data reveals that all-trans retinoic acid (ATRA) has anticancer effects on different types of tumor cells. However, data about the effects of ATRA on glioblastoma cells are contradictory. In this study, we examined whether ATRA treatment affects features of human glioblastoma U251 cells. To that end, the cells were treated with different concentrations of ATRA. Results obtained by MTT and the crystal violet assays imply that ATRA affected the viability of U251 glioblastoma cells in a dose- and time-dependent manner. Fluorescence staining of microtubule cytoskeleton protein ?-tubulin revealed that ATRA induced changes in cell morphology. Using semi-quantitative RT-PCR we found that the expression of SOX3 and GFAP genes, as markers of neural differentiation, was not changed upon ATRA treatment. Thus, the observed changes in cell morphology after ATRA treatment are not associated with neural differentiation of U251 glioblastoma cells. The scratch-wound healing assay revealed that ATRA changed the mode of U251 cell migration from collective to single cell motility. The cell-matrix adhesion assay demonstrated that the pharmacologically relevant concentration of ATRA lowered the cell-matrix adhesion capability of U251 cells. In conclusion, our results imply that further studies are needed before ATRA could be considered for the treatment of glioblastoma.

Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma

“…Additionally, the proliferation of GL-15 GBM cells was inhibited by two structurally related RARγ agonists, CD-437 and CD-2325 [ 402 ]. In vitro experiments using GBM cell lines demonstrated that ATRA might induce morphological changes, differentiation, apoptosis, change in the mode of cell migration and reduction in growth, proliferation, invasiveness and adhesion of these cells [ 403 , 404 , 405 , 406 ]. Additionally, ATRA increased the asymmetric cell division of GSCs isolated from the U87 GBM cell line [ 407 ], induced differentiation and decreased proliferation and invasiveness of U87 cancer stem-like cells [ 408 ], induced morphology changes, growth arrest and differentiation of GBM stem-like cells [ 409 ] and induced differentiation and apoptosis and reduced proliferation and self-renewal of neurospheres of GBM therapy-resistant cancer stem cells [ 410 ].…”