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. J. Microbiol. Biotechnol. -0001;31:. https://doi.org/10.4014/jmb.2109.09002">
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J. Microbiol. Biotechnol. -0001; 31(11):

Published online November 30, -0001 https://doi.org/10.4014/jmb.2109.09002

Copyright © The Korean Society for Microbiology and Biotechnology.

The Root Bark of Morus alba L. and Its Bioactive Ingredient, Ursolic Acid, Suppress the Proliferation of Multiple Myeloma Cells by Inhibiting the Wnt/β-catenin Pathway

Geu Rim Song1,4†, Yoon Jung Choi2†, Soo Jin Park3, Subeen Shin1,4, Giseong Lee5, Hui Ji Choi2, Do Yup Lee3, Gyu-Yong Song2* , Sangtaek Oh1,4*

These authors contributed equally to this work.

1Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea 2College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea 3Department of Agricultural Biotechnology, Center for Food and Bioconvergence, Research Institute for Agricultural and Life Sciences, Seoul National University, Seoul, Republic of Korea 4Department of Interdisciplinary program for Bio-health Convergence, Kookmin University, Seoul 02707, Republic of Korea 5College of General Education, Kookmin University, Seoul 02707, Republic of Korea

Correspondence to:Gyu-Yong Song,       gysong@cnu.ac.kr
Sangtaek Oh,           ohsa@kookmin.ac.kr

Received: September 1, 2021; Revised: September 22, 2021; Accepted: September 23, 2021

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 V-FITC-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: Morus alba L, Wnt/&beta,-catenin signaling, multiple myeloma, ursolic acid