Ilimaquinone and Ethylsmenoquinone, Marine Sponge Metabolites, Suppress the Proliferation of Multiple Myeloma Cells by Down-Regulating the Level of β-Catenin

Marine Drugs

Eunju Yun¹  MinKyun Na¹  Gyu-Yong Song¹  Ji Seon Kim²  Sangtaek Oh²  Seoyoung Park²  Dong-Eun Kim³  Soojin Yoon³  In Hyun Hwang⁴ 

[1] College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea;Department of Bio and Fermentation Convergence Technology, Kookmin University,Seoul 136-702, Korea;Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea;Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA;

关键词: ilimaquinone;    ethylsmenoquinone;    Wnt/β-catenin signaling;    multiple myeloma;   

DOI  :  10.3390/md12063231

来源: DOAJ

【 摘 要 】

Deregulation of Wnt/β-catenin signaling promotes the development of a broad range of human cancers, including multiple myeloma, and is thus a potential target for the development of therapeutics for this disease. Here, we used a cell-based reporter systemto demonstrate that ilimaquinone and ethylsmenoquinone (formerly smenorthoquinone), sesquiterpene-quinones from a marine sponge, inhibited β-catenin response transcription induced with Wnt3a-conditioned medium, by down-regulating the level of intracellularβ-catenin. Pharmacological inhibition of glycogen synthase kinase-3β did not abolish the ilimaquinone and ethylsmenoquinone-mediated β-catenin down-regulation. Degradation of β-catenin was consistently found in RPMI-8226 multiple myeloma cells after ilimaquinone and ethylsmenoquinone treatment. Ilimaquinone and ethylsmenoquinone repressed the expression of cyclin D1, c-myc, and axin-2, which are β-catenin/T-cell factor-dependent genes, and inhibited the proliferation of multiple myeloma cells. In addition, ilimaquinone and ethylsmenoquinone significantly induced G0/G1 cell cycle arrest and apoptosis in RPMI-8266 cells. These findings suggest that ilimaquinone and ethylsmenoquinone exert their anti-cancer activity by blocking the Wnt/β-catenin pathway and have significant potential as therapies for multiple myeloma.

【 授权许可】

Unknown