Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Root Bark of Morus alba L. and Its Bioactive Ingredient, Ursolic Acid, Suppress the Proliferation of Multiple Myeloma Cells by Inhibiting Wnt/β-Catenin Pathway

  • Song, Geu Rim (Department of Bio and Fermentation Convergence Technology, Kookmin University) ;
  • Choi, Yoon Jung (College of Pharmacy, Chungnam National University) ;
  • Park, Soo Jin (Department of Agricultural Biotechnology, Center for Food and Bioconvergence, Research Institute for Agricultural and Life Sciences, Seoul National University) ;
  • Shin, Subeen (Department of Bio and Fermentation Convergence Technology, Kookmin University) ;
  • Lee, Giseong (College of General Education, Kookmin University) ;
  • Choi, Hui Ji (College of Pharmacy, Chungnam National University) ;
  • Lee, Do Yup (Department of Agricultural Biotechnology, Center for Food and Bioconvergence, Research Institute for Agricultural and Life Sciences, Seoul National University) ;
  • Song, Gyu-Yong (College of Pharmacy, Chungnam National University) ;
  • Oh, Sangtaek (Department of Bio and Fermentation Convergence Technology, Kookmin University)
  • Received : 2021.09.01
  • Accepted : 2021.09.23
  • Published : 2021.11.28
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Abstract

The root bark of Morus alba L. has cytotoxic activity against several types of cancer cells. However, little is known about its chemopreventive mechanisms and bioactive metabolites. In this study, we showed that M. alba L. root bark extracts (MRBE) suppressed β-catenin response transcription (CRT), which is aberrantly activated in various cancers, by promoting the degradation of β-catenin. In addition, MRBE repressed the expression of the β-catenin/T-cell factor (TCF)-dependent genes, c-myc and cyclin D1, thus inhibiting the proliferation of RPMI-8226 multiple myeloma (MM) cells. MRBE induced apoptosis in MM cells, as evidenced by the increase in the population of annexin VFITC-positive cells and caspase-3/7 activity. We identified ursolic acid in MRBE through LC/mass spectrum (MS) and observed that it also decreased intracellular β-catenin, c-myc, and cyclin D1 levels. Furthermore, it suppressed the proliferation of RPMI-8226 cells by stimulating cell cycle arrest and apoptosis. These findings suggest that MRBE and its active ingredient, ursolic acid, exert antiproliferative activity by promoting the degradation of β-catenin and may have significant chemopreventive potential against MM.

Keywords

Acknowledgement

This work was supported by a Korea Environmental Industry and Technology Institute (KEITI) grant funded by the Ministry of Environment of Korea and by a research fund of Chungnam National University.

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