Zerumbone, a ginger sesquiterpene, inhibits migration, invasion, and metastatic behavior of human malignant glioblastoma multiforme in vitro.

in BioFactors (Oxford, England) by Mohammad Jalili-Nik, Amir R Afshari, Hamed Sabri, Bahram Bibak, Hamid Mollazadeh, Amirhossein Sahebkar

TLDR

  • Zerumbone, a natural phytochemical, suppresses GBM cell migration and invasion, inhibits MMP activity, and downregulates IL-1β and MCP-1 mRNA expression, offering a promising therapeutic strategy for GBM treatment.

Abstract

The most widespread and challenging aggressive malignant tumor in the brain is glioblastoma multiforme (GBM). GBM is characterized, in particular, by significant intratumor cell variability, high growth rates, and widespread invasiveness within the surrounding normal brain parenchyma. The present study aimed to examine the impact of the natural product Zerumbone, a promising sesquiterpenoid phytochemical from Zingiber zerumbet, on U-87 MG GBM cells and its underlying molecular mechanisms. At sub-lethal doses, Zerumbone exerted a concentration- and time-dependent suppression of cell migration ability utilizing scratch wound closure assay; it also inhibited GBM cells' invasion using Transwell invasion assay in a concentration-dependent fashion. The enzymatic activity of matrix metalloproteinase (MMP)-2/-9 and their protein expression has also been reduced by administration of Zerumbone. Furthermore, Zerumbone was revealed to downregulate the mRNA expression level of IL-1β and MCP-1, two genes contributing to MMPs expression. We also found that Zerumbone exerted an inhibitory effect on the expression of Akt and total p44/42 MAPK (Erk1/Erk2) against U-87 MG cells. These findings collectively provide further proof for the possible molecular signaling basis of the antimetastatic effects of Zerumbone as a promising phytochemical, indicating a therapeutic strategy for the treatment of GBM through repression of migration, invasion, and metastasis.

Overview

  • The study investigated the impact of Zerumbone, a natural sesquiterpenoid phytochemical, on glioblastoma multiforme (GBM) cells and its underlying molecular mechanisms.
  • Zerumbone was found to suppress GBM cells' migration and invasion abilities, inhibit matrix metalloproteinase (MMP) activity and protein expression, and downregulate mRNA expression levels of IL-1β and MCP-1.
  • The study aimed to identify a therapeutic strategy for the treatment of GBM through the repression of migration, invasion, and metastasis using Zerumbone.

Comparative Analysis & Findings

  • The study compared the effects of Zerumbone on U-87 MG GBM cells and found that it suppressed cell migration and invasion abilities in a concentration- and time-dependent manner.
  • The findings showed that Zerumbone reduced the enzymatic activity and protein expression of MMP-2/-9, and downregulated mRNA expression levels of IL-1β and MCP-1.
  • The study found that Zerumbone inhibited the expression of Akt and total p44/42 MAPK (Erk1/Erk2) against U-87 MG cells, providing evidence for its antimetastatic effects.

Implications and Future Directions

  • The study's findings suggest that Zerumbone could be a promising phytochemical for the treatment of GBM, particularly in reducing migration, invasion, and metastasis.
  • Further research is needed to fully understand the molecular mechanisms underlying Zerumbone's effects and to explore its potential therapeutic applications.
  • Future studies could investigate the efficacy and safety of Zerumbone in animal models of GBM and potentially in clinical trials.
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