A Promising Way to Overcome Temozolomide Resistance through Inhibition of Protein Neddylation in Glioblastoma Cell Lines
There is no effective therapy for the lately increased incidence of glioblastoma multiforme (GBM)—the most common primary brain tumor characterized by a high degree of invasiveness and genetic heterogeneity. Currently, DNA alkylating agent temozolomide (TMZ) is the standard chemotherapy. Nevertheles...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI
2023
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| Subjects: | |
| Online Access: | View Fulltext in Publisher View in Scopus |
| LEADER | 02837nam a2200517Ia 4500 | ||
|---|---|---|---|
| 001 | 10.3390-ijms24097929 | ||
| 008 | 230529s2023 CNT 000 0 und d | ||
| 020 | |a 16616596 (ISSN) | ||
| 245 | 1 | 0 | |a A Promising Way to Overcome Temozolomide Resistance through Inhibition of Protein Neddylation in Glioblastoma Cell Lines |
| 260 | 0 | |b MDPI |c 2023 | |
| 856 | |z View Fulltext in Publisher |u https://doi.org/10.3390/ijms24097929 | ||
| 856 | |z View in Scopus |u https://www.scopus.com/inward/record.uri?eid=2-s2.0-85159322297&doi=10.3390%2fijms24097929&partnerID=40&md5=562ad0fdc6c108f4c594e5ea53ac8a96 | ||
| 520 | 3 | |a There is no effective therapy for the lately increased incidence of glioblastoma multiforme (GBM)—the most common primary brain tumor characterized by a high degree of invasiveness and genetic heterogeneity. Currently, DNA alkylating agent temozolomide (TMZ) is the standard chemotherapy. Nevertheless, TMZ resistance is a major problem in the treatment of GBM due to numerous molecular mechanisms related to DNA damage repair, epigenetic alterations, cellular drug efflux, apoptosis-autophagy, and overactive protein neddylation. Low molecular weight inhibitors of NEDD8-activating enzyme (NAE), such as MLN4924, attenuate protein neddylation and present a promising low-toxicity anticancer agent. The aim of our study was to find an effective combination treatment with TMZ and MLN4924 in our TMZ-resistant GBM cell lines and study the effect of these combination treatments on different protein expressions such as O6-methylguanine methyltransferase (MGMT) and p53. The combination treatment successfully decreased cell viability and sensitized TMZ-resistant cells to TMZ, foreshadowing a new treatment strategy for GBM. © 2023 by the authors. | |
| 650 | 0 | 4 | |a alkylating agent |
| 650 | 0 | 4 | |a Antineoplastic Agents, Alkylating |
| 650 | 0 | 4 | |a Brain Neoplasms |
| 650 | 0 | 4 | |a brain tumor |
| 650 | 0 | 4 | |a Cell Line, Tumor |
| 650 | 0 | 4 | |a combination treatment |
| 650 | 0 | 4 | |a DNA ligase |
| 650 | 0 | 4 | |a DNA methyltransferase |
| 650 | 0 | 4 | |a DNA Modification Methylases |
| 650 | 0 | 4 | |a DNA Repair Enzymes |
| 650 | 0 | 4 | |a drug resistance |
| 650 | 0 | 4 | |a Drug Resistance, Neoplasm |
| 650 | 0 | 4 | |a genetics |
| 650 | 0 | 4 | |a glioblastoma |
| 650 | 0 | 4 | |a Glioblastoma |
| 650 | 0 | 4 | |a glioblastoma multiforme |
| 650 | 0 | 4 | |a human |
| 650 | 0 | 4 | |a Humans |
| 650 | 0 | 4 | |a metabolism |
| 650 | 0 | 4 | |a neddylation |
| 650 | 0 | 4 | |a pathology |
| 650 | 0 | 4 | |a pevonedistat |
| 650 | 0 | 4 | |a temozolomide |
| 650 | 0 | 4 | |a Temozolomide |
| 650 | 0 | 4 | |a tumor cell line |
| 700 | 1 | 0 | |a Berta, G. |e author |
| 700 | 1 | 0 | |a Brandt, B. |e author |
| 700 | 1 | 0 | |a Heffer, M. |e author |
| 700 | 1 | 0 | |a Németh, M. |e author |
| 700 | 1 | 0 | |a Pap, M. |e author |
| 700 | 1 | 0 | |a Rauch, T.A. |e author |
| 700 | 1 | 0 | |a Szünstein, M. |e author |
| 773 | |t International Journal of Molecular Sciences | ||