Geniposide exhibits anticancer activity to medulloblastoma cells by downregulating microRNA-373

J Biochem Mol Toxicol. 2020 May;34(5):e22471. doi: 10.1002/jbt.22471. Epub 2020 Feb 14.

Abstract

Background: Medulloblastoma is a common tumor originates from central nervous system in children with metastatic potential. Geniposide is the major active ingredient separated from the fruit of Gardenia jasminoides Ellis. Herein, we tested the possible anticancer activity of geniposide on human medulloblastoma cells, as well as the potential underlying molecular mechanisms.

Methods: Firstly, followed by geniposide incubation, cell viability, proliferation, apoptosis, migration, and invasion of medulloblastoma Daoy cells, along with microRNA-373 (miR-373) expression were tested, respectively. Then, the influences of miR-373 overexpression in the reduction of medulloblastoma cell proliferation, migration, and invasion and the elevation of apoptosis, triggered by geniposide treatment, were re-investigated. Finally, the Ras/Raf/MEK/ERK pathway activity was analyzed.

Results: Geniposide treatment inhibited medulloblastoma cell viability, proliferation, migration, and invasion, but promoted cell apoptosis. Surprisingly, miR-373 expression in medulloblastoma cells was obviously downregulated by geniposide treatment. miR-373 overexpression reversed the effects of geniposide on Daoy cells. Furthermore, geniposide hindered the Ras/Raf/MEK/ERK pathway by downregulating miR-373 expression.

Conclusion: Geniposide exhibited anticancer activity on human medulloblastoma cells and blocked Ras/Raf/MEK/ERK pathway by downregulating miR-373 expression.

Keywords: Ras/Raf/MEK/ERK pathway; cell metastasis; cell proliferation; geniposide; medulloblastoma; microRNA-373.

Publication types

  • Retracted Publication

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cerebellar Neoplasms / metabolism*
  • Cerebellar Neoplasms / pathology
  • Down-Regulation / drug effects*
  • Fruit / chemistry*
  • Gardenia / chemistry*
  • Humans
  • Iridoids / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • Medulloblastoma / metabolism*
  • Medulloblastoma / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Plant Extracts / pharmacology*
  • Transfection

Substances

  • Antineoplastic Agents
  • Iridoids
  • MIRN373 microRNA, human
  • MicroRNAs
  • Plant Extracts
  • geniposide