CKD-581 Downregulates Wnt/β-Catenin Pathway by DACT3 Induction in Hematologic Malignancy.
CKD-581
DACT3
HDAC
Hematologic cancer
Wnt/β-catenin pathway
Journal
Biomolecules & therapeutics
ISSN: 1976-9148
Titre abrégé: Biomol Ther (Seoul)
Pays: Korea (South)
ID NLM: 101472832
Informations de publication
Date de publication:
01 Sep 2022
01 Sep 2022
Historique:
received:
11
02
2022
revised:
10
05
2022
accepted:
20
05
2022
pubmed:
8
7
2022
medline:
8
7
2022
entrez:
7
7
2022
Statut:
ppublish
Résumé
The present study evaluated the anti-cancer activity of histone deacetylase (HDAC)-inhibiting CKD-581 in multiple myeloma (MM) and its pharmacological mechanisms. CKD-581 potently inhibited a broad spectrum of HDAC isozymes. It concentration-dependently inhibited proliferation of hematologic cancer cells including MM (MM.1S and RPMI8226) and T cell lymphoma (HH and MJ). It increased the expression of the dishevelled binding antagonist of β-catenin 3 (DACT3) in T cell lymphoma and MM cells, and decreased the expression of c-Myc and β-catenin in MM cells. Additionally, it enhanced phosphorylated p53, p21, cleaved caspase-3 and the subG1 population, and reversely, downregulated cyclin D1, CDK4 and the anti-apoptotic BCL-2 family. Finally, administration of CKD-581 exerted a significant anti-cancer activity in MM.1S-implanted xenografts. Overall, CKD-581 shows anticancer activity via inhibition of the Wnt/β-catenin signaling pathway in hematologic malignancies. This finding is evidence of the therapeutic potential and rationale of CKD-581 for treatment of MM.
Identifiants
pubmed: 35794797
pii: biomolther.2022.022
doi: 10.4062/biomolther.2022.022
pmc: PMC9424334
doi:
Types de publication
Journal Article
Langues
eng
Pagination
435-446Références
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