Dataset Information

Styryl Quinazolinones as Potential Inducers of Myeloid Differentiation via Upregulation of C/EBP?.

ABSTRACT: The CCAAT enhancer-binding protein ? (C/EBP?) plays an important role in myeloid cell differentiation and in the enhancement of C/EBP? expression/activity, which can lead to granulocytic differentiation in acute myeloid leukemia (AML) cells. We found that styryl quinazolinones induce upregulation of C/EBP? expression, and thereby induce myeloid differentiation in human myeloid leukemia cell lines. We screened a series of active styryl quinazolinones and evaluated the structure?activity relationship (SAR) of these small molecules in inducing C/EBP? expression-thereby prompting the leukemic cells to differentiate. We observed that compound 78 causes differentiation at 3 ?M concentration, while 1 induces differentiation at 10 ?M concentration. We also observed an increase in the expression of neutrophil differentiation marker CD11b upon treatment with 78. Both the C/EBP? and C/EBP? levels were found to be upregulated by treatment with 78. These SAR findings are inspiration to develop further modified styryl quinazolinones, in the path of this novel differentiation therapy, which can contribute to the care of patients with AML.

SUBMITTER: Sridhar R

PROVIDER: S-EPMC6222906 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Styryl Quinazolinones as Potential Inducers of Myeloid Differentiation via Upregulation of C/EBPα.

Sridhar Radhakrishnan R Takei Hisashi H Syed Riyaz R Kobayashi Ikei S IS Hui Liu Bee LB Kamal Ahmed A Tenen Daniel G DG Kobayashi Susumu S SS

Molecules (Basel, Switzerland) 20180803 8

The CCAAT enhancer-binding protein α (C/EBPα) plays an important role in myeloid cell differentiation and in the enhancement of C/EBPα expression/activity, which can lead to granulocytic differentiation in acute myeloid leukemia (AML) cells. We found that styryl quinazolinones induce upregulation of C/EBPα expression, and thereby induce myeloid differentiation in human myeloid leukemia cell lines. We screened a series of active styryl quinazolinones and evaluated the structure⁻activity relations ...[more]

PMID: 30081475

Similar Datasets

Project description:Long non-coding RNA HOTAIR has been reported to play a key role in regulating various biological processes in various cancers. However, the roles and mechanisms of HOTAIR in acute myeloid leukaemia (AML) are still unclear and need to be investigated. In this study, we induced differentiation of four AML cell lines by all-trans retinoic acid (ATRA) and found HOTAIR was significantly upregulated in the process. Chromatin immunoprecipitation (ChIP) assays indicated that C/EBPβ upregulated HOTAIR during ATRA induced differentiation in HL-60 cells. By gain- and loss-of-function analysis, we then observed that HOTAIR expression was positively correlated with ATRA-induced differentiation and negatively regulated G1 phase arrest in HL-60 cells. In addition, we found that HOTAIR promoted ATRA-induced differentiation via the regulation of the cell cycle regulator p21 via miR-17-5p. Moreover, we detected the expression of HOTAIR in 84 de novo AML patients, HOTAIR was found significantly downregulated in the AML patients compared to the iron deficiency anaemia (IDA) control group, negatively correlated with the platelet level in M2 patients. In all, our data suggest that HOTAIR may be subtype-specific in AML-M2 patients, also HOTAIR regulates AML differentiation by C/EBPBβ/HOTAIR/miR-17-5p/p21 pathway. The findings of the present study provide a novel insight into the mechanism of lncRNA-mediated differentiation and indicate that HOTAIR may be a promising therapeutic target for leukaemia, especially for AML with M2 type.Abbreviation: AML: acute myeloid leukaemia; APL: acute promyelocytic leukaemia; ATRA: all-trans retinoic acid; CCK8: cell Counting Kit-8; CDKs: cyclin-dependent kinases ; CeRNA: competing endogenous RNAs; ChIP: chromatin immunoprecipitation; CHX: cycloheximide; FAB: French-American-British; FCM: flow cytometry; HOTAIR: HOX transcript antisense RNA; IDA: iron-deficiency anemia; lncRNA: long non-coding RNA; 3'UTR: 3'untranslated region; MT: Mutation type; WT: Wild type; qRT-PCR: Quantitative real-time PCR.

Dataset Information

Styryl Quinazolinones as Potential Inducers of Myeloid Differentiation via Upregulation of C/EBP?.

Publications

Styryl Quinazolinones as Potential Inducers of Myeloid Differentiation via Upregulation of C/EBPα.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets