Valproic Acid Reduces Invasiveness and Cellular Growth in 2D and 3D Glioblastoma Cell Lines

Glioblastoma (GBM) is the most common malignant brain tumor, with a poor prognosis and low survival. Its treatment includes complete surgical resection followed by radiotherapy combined with temozolomide (TMZ). GBM contains glial stem cells (GSCs), which contribute to tumor progression, invasiveness, and drug resistance. The histone deacetylase (HDAC) inhibitor valproic acid (VA) has been shown to be a potent antitumor and cytostatic agent. In this study, we tested the effects of VA on glioma cell proliferation, migration, and apoptosis using T98G monolayer and spheroid cells. T98G and U-87MG glioblastoma cell viability was determined by MTT. Cell cycle and ROS levels were analyzed by flow cytometry, and gene and protein levels were detected, respectively, by RT-PCR and immunoblotting. VA reduces cell viability in 2D and 3D T98G and U-87MG cells and blocks the cell cycle at the G0/G1 with decreased levels of cyclin D1. VA addresses apoptosis and ROS production. In addition, VA significantly decreases the mRNA levels of the mesenchymal markers, and it counteracts cell migration, also decreasing MMP2. The results confirm the inhibitory effect of VA on the growth of the T98G and U-87MG cell lines and its ability to counteract migration in both 2D and 3D cellular models.