Honokiol suppresses renal cancer cells' metastasis via dual-blocking epithelial-mesenchymal transition and cancer stem cell properties through modulating miR-141/ZEB2 signaling

Mol Cells. 2014 May;37(5):383-8. doi: 10.14348/molcells.2014.0009. Epub 2014 May 8.

Abstract

Renal cell carcinoma (RCC) is associated with a high frequency of metastasis and only few therapies substantially prolong survival. Honokiol, isolated from Magnolia spp. bark, has been shown to exhibit pleiotropic anticancer effects in many cancer types. However, whether honokiol could suppress RCC metastasis has not been fully elucidated. In the present study, we found that honokiol suppressed renal cancer cells' metastasis via dual-blocking epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties. In addition, honokiol inhibited tumor growth in vivo. It was found that honokiol could upregulate miR-141, which targeted ZEB2 and modulated ZEB2 expression. Honokiol reversed EMT and suppressed CSC properties partly through the miR-141/ZEB2 axis. Our study suggested that honokiol may be a suitable therapeutic strategy for RCC treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Biphenyl Compounds / pharmacology*
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition / drug effects*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Lignans / pharmacology*
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • Tumor Burden
  • Zinc Finger E-box Binding Homeobox 2

Substances

  • Antineoplastic Agents, Phytogenic
  • Biphenyl Compounds
  • Homeodomain Proteins
  • Lignans
  • MIRN141 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • honokiol