RT Journal Article SR Electronic T1 Radiosensitization of Glioblastoma Cells by a Novel DNA Methyltransferase-inhibiting Phthalimido-Alkanamide Derivative JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 759 OP 769 DO 10.21873/anticanres.13173 VO 39 IS 2 A1 CHAN WOO WEE A1 JIN HO KIM A1 HAK JAE KIM A1 HYUN-CHEOL KANG A1 SOO YOUN SUH A1 BEOM SOO SHIN A1 EUNSOOK MA A1 IL HAN KIM YR 2019 UL http://ar.iiarjournals.org/content/39/2/759.abstract AB 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.