Wogonin suppresses the LPS-enhanced invasiveness of MDA-MB-231 breast cancer cells by inhibiting the 5-LO/BLT2 cascade

G. O. Ji-Hyun, Jun Dong Wei, Jae In Park, Kyung Seop Ahn, Jae-Hong Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Wogonin, a naturally occurring bioactive monoflavonoid isolated from Scutellariae radix (roots of Scutellariae baicalensis Georgi), has known anticancer effects. However, the molecular signaling mechanism by which wogonin inhibits invasiveness in breast cancer cells remains unclear. In the present study, it was observed that wogonin exerted an inhibitory effect on the lipopolysaccharide (LPS)-enhanced invasiveness of MDA-MB-231 cells. In addition, wogonin inhibited the synthesis of interleukin-8 (IL-8) and matrix metallopeptidase-9 (MMP-9), which are critical for promoting invasiveness in MDA-MB-231 cells. Wogonin also suppressed the expression of leukotriene B4 receptor 2 (BLT2) and the synthesis of its ligand, by inhibiting 5-lipoxygenase (5-LO) in LPS-stimulated MDA-MB-231 cells. Notably, wogonin attenuated the production of IL-8 and MMP-9 by inhibiting the BLT2/extra-cellular signal-regulated kinase (ERK)-linked cascade. Finally, in vivo, LPS-driven MDA-MB-231 cell metastasis was markedly suppressed by wogonin administration. Overall, the present results suggested that wogonin inhibited the 5-LO/BLT2/ERK/IL-8/MMP-9 signaling cascade and demonstrated that this cascade may be an important target through which wogonin exerts its anticancer effects in breast cancer.

Original languageEnglish
Pages (from-to)1899-1908
Number of pages10
JournalInternational Journal of Molecular Medicine
Volume42
Issue number4
DOIs
Publication statusPublished - 2018 Oct 1

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Arachidonate 5-Lipoxygenase
Lipopolysaccharides
Breast Neoplasms
Metalloproteases
Interleukin-8
Scutellaria baicalensis
Phosphotransferases
Leukotriene B4 Receptors
wogonin
Neoplasm Metastasis
Ligands

Keywords

  • 5-lipoxygenase
  • Breast cancer
  • Inteleukin-8
  • Invasiveness
  • Leuko- triene B4 receptor 2
  • Lipopolysaccharide
  • Matrix metallopeptidase-9
  • MDA-MB-231 cells
  • Metastasis
  • Wogonin

ASJC Scopus subject areas

  • Genetics

Cite this

Wogonin suppresses the LPS-enhanced invasiveness of MDA-MB-231 breast cancer cells by inhibiting the 5-LO/BLT2 cascade. / Ji-Hyun, G. O.; Wei, Jun Dong; Park, Jae In; Ahn, Kyung Seop; Kim, Jae-Hong.

In: International Journal of Molecular Medicine, Vol. 42, No. 4, 01.10.2018, p. 1899-1908.

Research output: Contribution to journalArticle

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abstract = "Wogonin, a naturally occurring bioactive monoflavonoid isolated from Scutellariae radix (roots of Scutellariae baicalensis Georgi), has known anticancer effects. However, the molecular signaling mechanism by which wogonin inhibits invasiveness in breast cancer cells remains unclear. In the present study, it was observed that wogonin exerted an inhibitory effect on the lipopolysaccharide (LPS)-enhanced invasiveness of MDA-MB-231 cells. In addition, wogonin inhibited the synthesis of interleukin-8 (IL-8) and matrix metallopeptidase-9 (MMP-9), which are critical for promoting invasiveness in MDA-MB-231 cells. Wogonin also suppressed the expression of leukotriene B4 receptor 2 (BLT2) and the synthesis of its ligand, by inhibiting 5-lipoxygenase (5-LO) in LPS-stimulated MDA-MB-231 cells. Notably, wogonin attenuated the production of IL-8 and MMP-9 by inhibiting the BLT2/extra-cellular signal-regulated kinase (ERK)-linked cascade. Finally, in vivo, LPS-driven MDA-MB-231 cell metastasis was markedly suppressed by wogonin administration. Overall, the present results suggested that wogonin inhibited the 5-LO/BLT2/ERK/IL-8/MMP-9 signaling cascade and demonstrated that this cascade may be an important target through which wogonin exerts its anticancer effects in breast cancer.",
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