DTCM-glutarimide Delays Growth and Radiosensitizes Glioblastoma

Abstract

Background and purpose: Glioblastoma (GBM) is the most aggressive brain tumor. Even with the advent of temozolomide, patient survival remains poor, with expected median survival around 1 year from diagnosis. Consequently, the relentless search for new therapeutic strategies able to increase patient outcome persists. 3-[(dodecylthiocarbonyl) methyl] glutarimide (DTCM-g) is a new anti-inflammatory compound that already showed antitumor effects.

Materials and methods: Clonogenic survival, proliferation, apoptosis, cell cycle progression and invasion capacity of pediatric and adult GBM cell lines (U87MG, U251MG, SF188 and KNS-42) were evaluated under treatment with DTCM-g. The combined treatment with radiation was also evaluated in vitro and in vivo through xerographic models.

Results: DTCM-g is able to impair proliferation, reduce clonogenic capacity and induce cell cycle arrest in GBM cell lines. No alteration in apoptosis rates was found after treatment. DTCM-g also reduces the invasion capacity of all GBM cell lines without alterations in MMP2 and uPa expression. Moreover, the drug radiosensitized GBM in vitro and in vivo.

Conclusion: Although additional studies are still necessary to support our findings, our results suggest that DTCM-g may be a promising drug on the adjuvant treatment of GBM exhibiting antitumor effects, especially through radiosensitization.

Keywords: DTCM-g; brain tumor; glioblastoma; invasion; radiation; radiosensitizing drug..