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

Background: Orientin (luteolin 8-C-beta-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 wellknown anticancer flavonoid, luteolin and luteolin 8-C-beta-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 (PKC alpha), 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 PKC alpha 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.