Tytuł
Revealing the epigenetic effect of temozolomide on glioblastoma cell lines in therapeutic conditions
Autorzy
[ 1 ] Instytut Chemii Bioorganicznej Polskiej Akademii Nauk, Polska Akademia Nauk | [ P ] pracownik
Dyscyplina naukowa (Ustawa 2.0)
Rok publikacji
2020
Typ artykułu
artykuł naukowy
Język publikacji
angielski
Słowa kluczowe
Streszczenie
EN Temozolomide (TMZ) is a drug of choice in glioblastoma treatment. Its therapeutic applications expand also beyond high grade gliomas. However, a significant number of recurrences and resistance to the drug is observed. The key factor in each chemotherapy is to achieve the therapeutic doses of a drug at the pathologic site. Nonetheless, the rate of temozolomide penetration from blood to cerebrospinal fluid is only 20-30%, and even smaller into brain intestinum. That makes a challenge for the therapeutic regimens to obtain effective drug concentrations with minimal toxicity and minor side effects. The aim of our research was to explore a novel epigenetic mechanism of temozolomide action in therapeutic conditions. We analyzed the epigenetic effects of TMZ influence on different glioblastoma cell lines in therapeutically achieved TMZ concentrations through total changes of the level of 5-methylcytosine in DNA, the main epigenetic marker. That was done with classical approach of radioactive nucleotide post-labelling and separation on thin-layer chromatography. In the range of therapeutically achieved temozolomide concentrations we observed total DNA hypomethylation. The significant hypermethylating effect was visible after reaching TMZ concentrations of 10-50 mu M (depending on the cell line). Longer exposure time promoted DNA hypomethylation. The demethylated state of the glioblastoma cell lines was overcome by repeated TMZ applications, where dosedependent increase in DNA 5-methylcytosine contents was observed. Those effects were not seen in non-cancerous cell line. The increase of DNA methylation resulting in global gene silencing and consecutive down regulation of gene expression after TMZ treatment may explain better glioblastoma patients' survival.
Strony (od-do)
e0229534
Typ licencji
CC BY-ND (uznanie autorstwa - bez utworów zależnych)
Wersja tekstu w otwartym dostępie
ostateczna wersja opublikowana
Data udostępnienia
02.2020
Czas udostępnienia publikacji w sposób otwarty
w momencie opublikowania
Punktacja Ministerstwa / czasopismo
100
Punktacja Ministerstwa / czasopismo w ewaluacji 2017-2021
100
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