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Mar. Drugs 2014, 12(6), 3231-3244; https://doi.org/10.3390/md12063231

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

1
Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Korea
2
College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea
3
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
4
Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 11 December 2013 / Revised: 15 April 2014 / Accepted: 13 May 2014 / Published: 28 May 2014
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Abstract

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 system to 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 intracellular β-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. View Full-Text
Keywords: ilimaquinone; ethylsmenoquinone; Wnt/β-catenin signaling; multiple myeloma ilimaquinone; ethylsmenoquinone; Wnt/β-catenin signaling; multiple myeloma
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Park, S.; Yun, E.; Hwang, I.H.; Yoon, S.; Kim, D.-E.; Kim, J.S.; Na, M.; Song, G.-Y.; Oh, S. Ilimaquinone and Ethylsmenoquinone, Marine Sponge Metabolites, Suppress the Proliferation of Multiple Myeloma Cells by Down-Regulating the Level of β-Catenin. Mar. Drugs 2014, 12, 3231-3244.

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