Title:DTCM-glutarimide Delays Growth and Radiosensitizes Glioblastoma
VOLUME: 18 ISSUE: 9
Author(s):Gabriela Molinari Roberto, Helder Henrique Paiva, Lucas Eduardo Botelho de Souza, Julia Alejandra Pezuk, Gabriela Maciel Vieira, Harley Francisco de Oliveira, Kazuo Umezawa, Luiz Gonzaga Tone and María Sol Brassesco*
Affiliation:Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, University of Sao Paulo, Department of Internal Medicine, Ribeirao Preto School of Medicine, University of Sao Paulo, Regional Blood Center of Ribeirao Preto, Ribeirao Preto School of Medicine, University of Sao Paulo, Department of Genetics, Ribeirao Preto School of Medicine, University of Sao Paulo, Department of Genetics, Ribeirao Preto School of Medicine, University of Sao Paulo, Department of Anatomy, Ribeirao Preto School of Medicine, University of Sao Paulo, Department of Pediatrics, Ribeirão Preto School of Medicine, University of São Paulo, Department of Molecular Target Medicine, Aichi Medical University School of Medicine, Aichi, Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, University of Sao Paulo
Keywords:DTCM-g, brain tumor, glioblastoma, radiation, radiosensitizing drug, invasion.
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.
