Smenospongidine suppresses the proliferation of multiple myeloma cells by promoting CCAAT/enhancer-binding protein homologous protein-mediated β-catenin degradation
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.
KeywordsSmenospongidine β-catenin degradation Multiple myeloma CCAAT/enhancer-binding protein homologous protein (CHOP)
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.
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Conflict of interest
The authors declare that there are no conflicts of interest.
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