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

J Microbiol Biotechnol. 2021 Nov 28;31(11):1559-1567. doi: 10.4014/jmb.2109.09002.

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, cmyc 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: Morus alba L.; Wnt/β-catenin signaling; multiple myeloma; ursolic acid.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin D1
  • Humans
  • Morus / chemistry*
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / pathology*
  • Plant Bark / chemistry
  • Plant Roots / chemistry
  • Proto-Oncogene Proteins c-myc
  • Triterpenes / pharmacology*
  • Wnt Signaling Pathway / drug effects
  • beta Catenin

Substances

  • Antineoplastic Agents, Phytogenic
  • CCND1 protein, human
  • CTNNB1 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Triterpenes
  • beta Catenin
  • Cyclin D1
  • ursolic acid