Anti-proliferative activity of CGK012 against multiple myeloma cells via Wnt/β-catenin signaling attenuation. (September 2017)

• Record Type: Journal Article
• Authors: Choi, Pyung jun; O, Yuseok; Her, Jin-Hyuk; Yun, Eunju; Song, Gyu Yong; Oh, Sangtaek
• Is Part Of: Leukemia research. Volume 60(2017:Sep.)
• Page Start: 103
• Page End: 108
• Publication Date: 2017-09
• Subjects: CGK012 -- Wnt/β-catenin signaling -- Protein degradation -- Multiple myeloma; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2017.07.001
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: CGK012, a pyranocoumarin compound, suppresses the Wnt/β-catenin pathway. CGK012 promotes N-terminal β-catenin phosphorylation and degradation. CGK012 inhibits the proliferation of multiple myeloma cells. CGK012 induces the apoptosis of multiple myeloma cells. Abstract: The aberrant activation of Wnt/β-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 β-catenin response transcription. CGK012 induced β-catenin phosphorylation at Ser33/Ser37/Thr41, leading to proteasomal degradation and reducing the level of intracellular β-catenin. Furthermore, CGK012 consistently decreased the amount of β-catenin and repressed the expression of cyclin D1, c-myc, and axin-2 (downstream target genes of β-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/β-catenin pathway; thus, it may have potential as a therapeutic agent for multiple myeloma treatment.