DTCM-glutarimide Delays Growth and Radiosensitizes Glioblastoma

Author(s)

Roberto, Gabriela Molinari ^[1] ; Paiva, Helder Henrique ^[2] ; Botelho de Souza, Lucas Eduardo ^[3] ; Pezuk, Julia Alejandra ^[4] ; Vieira, Gabriela Maciel ^[4] ; de Oliveira, Harley Francisco ^[5] ; Umezawa, Kazuo ^{[6, 7]} ; Tone, Luiz Gonzaga ; Brassesco, Maria Sol ^[1]

Affiliation

^[1] Univ Sao Paulo, Sci & Letters Ribeirao Preto, Fac Philosophy, Dept Biol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Internal Med, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Sch Med, Reg Blood Ctr Ribeirao Preto, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Genet, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Anat, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Pediat, Sao Paulo - Brazil

^[7] Aichi Med Univ, Sch Med, Dept Mol Target Med, Aichi - Japan

• Document type: Journal article
• Source: ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY; v. 18, n. 9, p. 1323-1329, 2018.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 13/23239-9 - Evaluation of the antitumor effects of the inhibition in vitro of the AP-1 transcription factor by DTCM-g in adult and pediatric glioblastoma
• Grantee: Gabriela Molinari Roberto
• Support Opportunities: Scholarships in Brazil - Scientific Initiation