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 language | English |
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Pages (from-to) | 1899-1908 |
Number of pages | 10 |
Journal | International journal of molecular medicine |
Volume | 42 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2018 Oct |
Bibliographical note
Funding Information:This work was supported by the Bio & Medical Technology Development Program (grant no. 2017M3A9D8063317), and a Mid‑Career Researcher Program (grant no. 2017R1A2B4002203), provided by the National Research Foundation funded by the Ministry of Science, Information and Communication Technologies and Future Planning, Republic of Korea. This work was also supported by Basic Science Research (grant no. 2015R1D1A1A01057757) through an NRF funded by the Ministry of Education, Republic of Korea and the BK21 Plus Program (School of Life Sciences and Biotechnology, Korea University).
Publisher Copyright:
© 2018 Spandidos Publications. All rights reserved.
Keywords
- 5-lipoxygenase
- Breast cancer
- Inteleukin-8
- Invasiveness
- Leuko- triene B4 receptor 2
- Lipopolysaccharide
- MDA-MB-231 cells
- Matrix metallopeptidase-9
- Metastasis
- Wogonin
ASJC Scopus subject areas
- Genetics