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Archives of Pharmacal Research

, Volume 40, Issue 5, pp 592–600 | Cite as

Smenospongidine suppresses the proliferation of multiple myeloma cells by promoting CCAAT/enhancer-binding protein homologous protein-mediated β-catenin degradation

  • Seoyoung Park
  • In Hyun Hwang
  • Jiseon Kim
  • Young-Hwa Chung
  • Gyu-Young Song
  • MinKyun NaEmail author
  • Sangtaek OhEmail author
Research Article

Abstract

Abnormal up-regulation of β-catenin expression is associated with the development and progression of multiple myeloma and is thus a potential therapeutic target. Here, we screened cell-based natural compounds and identified smenospongidine, a metabolite isolated from a marine sponge, as an antagonist of the Wnt/β-catenin signaling pathway. Smenospongidine promoted the degradation of intracellular β-catenin that accumulated via Wnt3a or 6-bromoindirubin-3′-oxime, an inhibitor of glycogen synthase kinase-3β. Consistently, smenospongidine down-regulated β-catenin expression and repressed the levels of β-catenin/T cell factor-dependent genes such as axin2, c-myc, and cyclin D1 in RPMI-8226 multiple myeloma cells. Smenospongidine suppressed proliferation and significantly induced apoptosis in RPMI-8266 cells. In addition, smenospongidine-induced β-catenin degradation was mediated by up-regulating CCAAT/enhancer-binding protein homologous protein (CHOP). These findings indicate that smenospongidine exerts its anti-proliferative activity by blocking the Wnt/β-catenin signaling pathway and may be a potential chemotherapeutic agent against multiple myeloma.

Keywords

Smenospongidine β-catenin degradation Multiple myeloma CCAAT/enhancer-binding protein homologous protein (CHOP) 

Notes

Acknowledegements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korean government (NRF-2015R1A2A2A01004599, NRF-2014R1A2A2A01006793) and the High Value-added Food Technology Development Program (114030-3) funded by the Ministry of Agriculture, Food and Rural Affairs.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

12272_2017_906_MOESM1_ESM.pptx (64 kb)
Supplementary material 1 (PPTX 63 kb)

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Copyright information

© The Pharmaceutical Society of Korea 2017

Authors and Affiliations

  • Seoyoung Park
    • 1
  • In Hyun Hwang
    • 2
  • Jiseon Kim
    • 1
  • Young-Hwa Chung
    • 3
  • Gyu-Young Song
    • 4
  • MinKyun Na
    • 4
    Email author
  • Sangtaek Oh
    • 1
    • 5
    Email author
  1. 1.Department of Bio and Fermentation Convergence Technology, BK21 PLUS programKookmin UniversitySeoulRepublic of Korea
  2. 2.College of PharmacyWoosuk UniversityWanjuRepublic of Korea
  3. 3.BK21+, Department of Cogno-Mechatronics EngineeringPusan National UniversityBusanRepublic of Korea
  4. 4.College of PharmacyChungnam National UniversityDaejeonRepublic of Korea
  5. 5.Department of Bio and Fermentation Convergence TechnologyKookmin UniversitySeoulRepublic of Korea

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