PUBLICATION
Synthetic flavagline derivative 1-chloroacetylrocaglaol promotes apoptosis in K562 erythroleukemia cells through miR-17-92 cluster genes
- Authors
- Wu, X., Yang, X., Varier, K.M., Rao, Q., Song, J., Huang, L., Huang, Y., Gajendran, B., He, Z., Yuan, C., Li, Y.
- ID
- ZDB-PUB-221018-24
- Date
- 2022
- Source
- Archiv der Pharmazie 355(12): e2200367 (Journal)
- Registered Authors
- He, Zhi-Xu
- Keywords
- BIM, c-MYC, chronic myeloid leukemia, megakaryocyte differentiation, miR-17-92
- MeSH Terms
-
- Animals
- Apoptosis
- Cell Proliferation
- Humans
- K562 Cells
- Leukemia, Erythroblastic, Acute*/drug therapy
- Leukemia, Erythroblastic, Acute*/genetics
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive*/drug therapy
- MicroRNAs*/genetics
- MicroRNAs*/metabolism
- MicroRNAs*/pharmacology
- Structure-Activity Relationship
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 36216575 Full text @ Arch. Pharm. (Weinheim)
Citation
Wu, X., Yang, X., Varier, K.M., Rao, Q., Song, J., Huang, L., Huang, Y., Gajendran, B., He, Z., Yuan, C., Li, Y. (2022) Synthetic flavagline derivative 1-chloroacetylrocaglaol promotes apoptosis in K562 erythroleukemia cells through miR-17-92 cluster genes. Archiv der Pharmazie. 355(12):e2200367.
Abstract
Chronic myeloid leukemia accounts for human deaths worldwide and could enhance sevenfold by 2050. Thus, the treatment regimen for this disorder is highly crucial at this time. Flavaglines are a natural class of cyclopentane benzofurans exhibiting various bioactivities like anticancer action. Despite the antiproliferative activity of flavaglines against diverse cancer cells, their roles and mechanism of action in chronic myeloid leukemia (CML) remain poorly understood. Thus, this study examines the antiproliferative effect of a newly synthesized flavagline derivative, 1-chloracetylrocaglaol (A2074), on erythroleukemia K562 cells and the zebrafish xenograft model. The study revealed that A2074 could inhibit proliferation, promote apoptosis, and boost megakaryocyte differentiation of K562 cells. This flavagline downregulated c-MYC and miR-17-92 cluster genes, targeting upregulation of the apoptotic protein Bcl-2-like protein 11 (BIM). The work uncovered a critical role of the c-MYC-miR-17-92-BIM axis in the growth and survival of CML cells.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping