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

Authors
Go, Ji-HyunWei, Jun-DongPark, Jae-InAhn, Kyung-SeopKim, Jae-Hong
Issue Date
10월-2018
Publisher
SPANDIDOS PUBL LTD
Keywords
wogonin; lipopolysaccharide; breast cancer; MDA-MB-231 cells; invasiveness; metastasis; 5-lipoxygenase; leukotriene B4 receptor 2; inteleukin-8; matrix metallopeptidase-9
Citation
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, v.42, no.4, pp.1899 - 1908
Indexed
SCIE
SCOPUS
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume
42
Number
4
Start Page
1899
End Page
1908
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/72580
DOI
10.3892/ijmm.2018.3776
ISSN
1107-3756
Abstract
Wogonin, a naturally occurring bioactivc 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 interlcukin-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/extracellular 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/ERKIIL-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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