Anti-proliferative activity of CGK012 against multiple myeloma cells via Wnt/ß-catenin signaling attenuation.
Leuk Res
; 60: 103-108, 2017 09.
Article
in En
| MEDLINE
| ID: mdl-28772205
ABSTRACT
The aberrant activation of Wnt/ß-catenin signaling is involved in the development of multiple myeloma; thus, this signaling pathway is a potential target for the development of therapeutics for this malignancy. Here, we performed cell-based chemical screening and found that CGK012, a pyranocoumarin compound, suppressed the Wnt3a-CM-mediated activation of ß-catenin response transcription. CGK012 induced ß-catenin phosphorylation at Ser33/Ser37/Thr41, leading to proteasomal degradation and reducing the level of intracellular ß-catenin. Furthermore, CGK012 consistently decreased the amount of ß-catenin and repressed the expression of cyclin D1, c-myc, and axin-2 (downstream target genes of ß-catenin) in RPMI-8226 multiple myeloma cells. In addition, CGK012 inhibited the proliferation of RPMI-8226 cells and promoted apoptosis, as indicated by the increase in the population of Annexin V-FITC-stained cells and caspase-3/7 activity. These findings suggest that CGK012 could exert antiproliferative activity against multiple myeloma cells by attenuating the Wnt/ß-catenin pathway; thus, it may have potential as a therapeutic agent for multiple myeloma treatment.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carbamates
/
Coumarins
/
Pyranocoumarins
/
Cell Proliferation
/
Beta Catenin
/
Wnt Signaling Pathway
/
Multiple Myeloma
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Leuk Res
Year:
2017
Document type:
Article