Anticancer research · 2019
Radiosensitization of Glioblastoma Cells by a Novel DNA Methyltransferase-inhibiting Phthalimido-Alkanamide Derivative.
СтатьяНазвание и аннотация: Перевод в очереди
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Wee Chan Woo, Kim Jin Ho, Kim Hak Jae, Kang Hyun-Cheol, Suh Soo Youn, Shin Beom Soo, Ma Eunsook, Kim Il Han
Аннотация
BACKGROUND/AIM: Strategies to enhance the therapeutic ratio of radiotherapy in glioblastoma are warranted. Our aim was to report a novel DNA methyltransferase inhibitor as a potential radiosensitizing agent in glioblastoma.
MATERIALS AND METHODS: Four glioblastoma cell lines and one normal astrocyte cell line were incubated with a newly-synthetized phthalimido-alkanamide derivative, MA17, and its radiosensitizing effects were assessed. We performed a tumor growth delay assay in two glioblastoma lines: U87MG and U138MG. We evaluated DNA methyltransferase (DNMT) inhibition, apoptosis, autophagy, DNA damage repair, and FANCA expression.
RESULTS: MA17 radiosensitized all glioblastoma cells (all p<0.05), but it did not affect normal astrocytes (p=0.193). MA17 significantly prolonged the mean tumor doubling time in vivo, in cells treated in addition with radiotherapy, compared to radiotherapy alone (p<0.05). DNMT activity was down-regulated, and apoptosis and autophagy were induced by MA17. Double-stranded DNA break foci were observed for prolonged periods in cells treated with MA17. FANCA expression was also inhibited.
CONCLUSION: A novel phthalimido-alkanamide derivative demonstrated significant radiosensitization in glioblastoma cells in vitro and in vivo. Further investigation is needed to translate these results to the clinic.
MATERIALS AND METHODS: Four glioblastoma cell lines and one normal astrocyte cell line were incubated with a newly-synthetized phthalimido-alkanamide derivative, MA17, and its radiosensitizing effects were assessed. We performed a tumor growth delay assay in two glioblastoma lines: U87MG and U138MG. We evaluated DNA methyltransferase (DNMT) inhibition, apoptosis, autophagy, DNA damage repair, and FANCA expression.
RESULTS: MA17 radiosensitized all glioblastoma cells (all p<0.05), but it did not affect normal astrocytes (p=0.193). MA17 significantly prolonged the mean tumor doubling time in vivo, in cells treated in addition with radiotherapy, compared to radiotherapy alone (p<0.05). DNMT activity was down-regulated, and apoptosis and autophagy were induced by MA17. Double-stranded DNA break foci were observed for prolonged periods in cells treated with MA17. FANCA expression was also inhibited.
CONCLUSION: A novel phthalimido-alkanamide derivative demonstrated significant radiosensitization in glioblastoma cells in vitro and in vivo. Further investigation is needed to translate these results to the clinic.
Предметные рубрики MeSH
AlkanesAnimalsApoptosisAstrocytesAutophagyCell Line, TumorCell SurvivalDNA (Cytosine-5-)-Methyltransferase 1DNA Breaks, Double-StrandedDNA RepairFanconi Anemia Complementation Group A ProteinFemaleGene Expression Regulation, NeoplasticGlioblastomaHumansMiceMice, Inbred BALB CMice, NudeNeoplasm TransplantationPhthalimidesRadiation ToleranceRadiation-Sensitizing Agents