Epigenetic targeting of glioma stem cells: Short-term and long-term treatments with valproic acid modulate DNA methylation and differentiation behavior, but not temozolomide sensitivity

摘要: Glioblastoma (GBM) is the most aggressive tumor of central nervous system. GBM a fatal tumor, incurable by conventional therapies. One factors underlying recurrence and poor long-term survival presence cancer stem-like cell population, termed glioma stem cells (GSCs), which particularly resistant to chemotherapy radiotherapy supports self-renewal. The aim present study was evaluate impact difference in effects short-term long‑term treatments with valproic acid (VPA), histone deacetylase inhibitor, on seven GSC lines. We investigated for first time changes genome-wide DNA methylation profile differentiation behavior GSCs induced VPA treatments. Moreover, we verified sensitivity after pretreatment and, notably, results provide evidence subpopulation more further Finally, since treatment reversal MGMT status, aimed sensitize temozolomide, drug commonly used this using regimen. overall data highlighted heterogeneous lines that representative heterogeneity GBM. were variable among these terms pro‑differentiating ability switch. Here, attempted identify suitable therapy eradication subpopulation, mandatory achieve an effective tumor. Differentiation-inducing epigenetic therapies are promising approaches affect multiple properties finally, defeat