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Title 

Orientin inhibits invasion by suppressing MMP-9 and IL-8 expression via the PKCα/ ERK/AP-1/STAT3-mediated signaling pathways in TPA-treated MCF-7 breast cancer cells

Authors 

S J KimT H PhamY BakHyung Won RyuSei-Ryang OhD Y Yoon

Publisher 

Elsevier

Issue Date 

2018

Citation 

Phytomedicine

Keywords 

AP-1ERKIL-8InvasionMMP-9STAT3

Abstract 

BACKGROUND: Orientin (luteolin 8-C-β-D-glucopyranoside), a glycosyl dietary flavonoid, has therapeutic effects such as anti-inflammation and antiadipogenesis. However, there is little known about the antimigratory and anti-invasive effects of orientin. Thus, we demonstrate the anti-invasive effects of orientin compared with well-known anticancer flavonoid, luteolin and luteolin 8-C-β-fucopyranoside (LU8C-FP). PURPOSE: We investigated whether orientin would inhibit the migration and invasion of 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced MCF-7 breast cancer cells. METHODS: We investigated the anti-invasive mechanism of orientin by using wound-healing assay, Matrigel invasion assay, gelatin zymography, qRT-PCR, ELISA, western blotting, nuclear, membrane and cytosolic fractionations, and immunofluorescence staining in MCF-7 cell line. RESULTS: We demonstrated the antimigratory and anti-invasive effects of orientin in TPA-treated MCF-7 cells. TPA-induced membrane translocation of protein kinase C alpha (PKCα), phosphorylation of extracellular signal regulated kinase (ERK), and nuclear translocations of activator protein-1 (AP-1) and signal transducer and activator of transcription 3 (STAT3) were downregulated by orientin. In addition, orientin also inhibited matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) expression. CONCLUSION: Orientin inhibits migratory and invasive responses by suppressing MMP-9 and IL-8 expression through mitigation of TPA-induced PKCα and ERK activation, as well as the nuclear translocation of AP-1 and STAT3. Therefore, orientin prevents tumor invasion and could be applied as a possible therapeutic agent for the treatment of cancer metastasis.

ISSN 

0944-7113

Link 

http://dx.doi.org/10.1016/j.phymed.2018.09.172

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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