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.
Highlights
Gliomas are the most common type of primary brain tumors in humans [1]
The number of metabolically active cells (MTT assay) (Fig. 1A) and the total number of live adherent cells (CV assay) (Fig. 1B) were analyzed. Both MTT and crystal violet (CV) assays imply that all-trans retinoic acid (ATRA) affected the viability of U251 glioblastoma cells in a dose- and time-dependent manner as compared to their untreated counterparts
The effect of ATRA on neural differentiation of U251 glioblastoma cells Bearing in mind that alternations in cell morphology could be associated with differentiation and that
Summary
Grade IV of glioma tumors, glioblastoma (GBM), is one of the most aggressive and deadly forms of cancer with a median survival of 15 months despite intensive therapeutic strategies which include surgical resection combined with radiotherapy and temozolomide chemotherapy [2,3,4]. All-trans retinoic acid (ATRA) is the most potent natural derivative of vitamin A that regulates various cell processes, including proliferation, differentiation and apoptosis of different normal and malignant cell types [9,10]. This compound has been shown to have anticancer effects on several types
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