The Effect of 3'-Hydroxy-3,4,5,4'-Tetramethoxy -stilbene, the Metabolite of the Resveratrol Analogue DMU-212, on the Motility and Proliferation of Ovarian Cancer Cells

Int J Mol Sci. 2020 Feb 7;21(3):1100. doi: 10.3390/ijms21031100.

Abstract

Targeting tumor cell motility and proliferation is an extremely important challenge in the prevention of metastasis and improving the effectiveness of cancer treatment. We recently published data revealing that DMU-214, the metabolite of firmly cytotoxic resveratrol analogue DMU-212, exerted significantly higher biological activity than the parent compound in ovarian cancer cells. The aim of the present study was to assess the molecular mechanism of the potential anti-migration and anti-proliferative effect of DMU-214 in ovarian cancer cell line SKOV-3. We showed that DMU-214 reduced the migratory capacity of SKOV-3 cells. The microarray analysis indicated ontology groups of genes involved in processes of negative regulation of cell motility and proliferation. Furthermore, we found DMU-214 triggered changes in expression of several migration- and proliferation-related genes (SMAD7, THBS1, IGFBP3, KLF4, Il6, ILA, SOX4, IL15, SRF, RGCC, GPR56) and proteins (GPR56, RGCC, SRF, SMAD7, THBS1), which have been shown to interact to each other to reduce cell proliferation and motility. Our study showed for the first time that DMU-214 displayed anti-migratory and anti-proliferative activity in SKOV-3 ovarian cancer cells. On the basis of whole transcriptome analysis of these cells, we provide new insight into the role of DMU-214 in inhibition of processes related to metastasis.

Keywords: DMU-214; migration; ovarian cancer; proliferation; resveratrol analogue.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Female
  • Humans
  • Kruppel-Like Factor 4
  • Ovarian Neoplasms / metabolism*
  • Resveratrol / analogs & derivatives*
  • Stilbenes / metabolism
  • Stilbenes / pharmacology*
  • Transcriptome

Substances

  • 3,4,5,4'-tetramethoxystilbene
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Stilbenes
  • Resveratrol