Effect of Arsenic Trioxide on Acute T-Lymphocytic Leukemia and DNA methyltransferase 1
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2022.0310
- VernacularTitle:三氧化二砷对T急淋白血病及DNA转甲基酶1的影响
- Author:
Jia-yin SU
1
;
Zhong-dao WU
2
;
Xue-qun LUO
1
Author Information
1. Department of Paediatrics， The First Affiliated Hospital， Sun Yat-sen University， Guangzhou 510080， China
2. Department of Parasitology， Zhongshan School of Medicine， Sun Yat-sen University// Key Laboratory of Tropical Disease Control， Sun Yat-sen University， Ministry of Education， Guangzhou 510080， China
- Publication Type:Journal Article
- Keywords:
acute leukemia;
cell death;
arsenic trioxide;
DNA methyltransferase 1
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2022;43(3):422-429
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effect of arsenic trioxide （ATO） on the expression of DNA methyltransferase 1 （DNMT1） and its anti-leukemia mechanism in acute T-lymphocytic leukemia （T-ALL） cells. MethodsT-ALL cell lines （Jurkat， CCRF-CEM， Molt-4） were cultured in vitro and divided into control （0 μmol/L）， low concentration （3 μmol/L） and high concentration （6 μmol/L） groups according to the dose of ATO， and the expression of DNMT1 and cleaved-caspase-3 were investigated by RT-qPCR and western blot after ATO treatment for 24 h （0， 3 and 6 μmol/L） intervention； Flow cytometry was applied to detect cell death in T-ALL cell lines （Jurkat， CCRF-CEM， MOLT-4）； The expression of DNMT1 and cleaved-caspase-3 and cell death were detected after applying ATO and Z-DEVD-FMK （caspase-3 specific inhibitor）； T-ALL cell death was detected after overexpressing DNMT1 under ATO intervention. ResultsWith the dose of ATO increasing， the expression level of DNMT1 in T-ALL cells decreased， the expression level of cleaved-caspase-3 protein increased， and the cell mortality increased （P<0.05）； The application of Z-DEVD-FMK specifically inhibited cleaved-caspase-3， diminished the inhibitory effect of ATO on DNMT1 expression， and decreased the cell mortality （P<0.05）；Overexpression of DNMT1 in T-ALL cells significantly reduced cell death induced by ATO treatment （P<0.05）. ConclusionWithin a certain concentration range， ATO effectively down-regulates the expression of DNMT1 via the activation of caspase-3 in a dose-dependent manner， thus inducing cell death in T-ALL cells， which provides a theoretical basis for the future application of ATO as a demethylating drug to improve the clinical treatment of T-ALL.
