Resveratrol Modulates MED28 (Magicin/EG-1) Expression and Inhibits Epidermal Growth Factor (EGF)-Induced Migration in MDA-MB-231 Human Breast Cancer Cells

Abstract

Resveratrol and pterostilbene exhibit diverse biological activities. MED28, a subunit of the mammalian Mediator complex for transcription, was also identified as magicin, an actin cytoskeleton Grb2-associated protein, and as endothelial-derived gene (EG-1). Several tumors exhibit aberrant MED28 expression, whereas the underlying mechanism is unclear. Triple-negative breast cancers, often expressing epidermal growth factor (EGF) receptor (EGFR), are associated with metastasis and poor survival. The objective of this study is to compare the effect of resveratrol and pterostilbene and to investigate the role of MED28 in EGFR-overexpressing MDA-MB-231 breast cancer cells. Pretreatment of resveratrol, but not pterostlbene, suppressed EGF-mediated migration and expression of MED28 and matrix metalloproteinase (MMP)-9 in MDA-MB-231 cells. Moreover, overexpression of MED28 increased migration, and the addition of EGF further enhanced migration. Our data indicate that resveratrol modulates the effect of MED28 on cellular migration, presumably through the EGFR/phosphatidylinositol 3-kinase (PI3K) signaling pathway, in breast cancer cells.

Resveratrol induces MMP-9 and cell migration via the p38 kinase and PI-3K pathways in HT1080 human fibrosarcoma cells

“…Moreover, resveratrol has been demonstrated to modulate MED28 (magicin/EG-1) expression and inhibit epidermal growth factor (EGF)-induced migration in MDA-MB-231 human breast cancer cells. The role of MED28 in cell migration reinforces the importance of this multifaceted protein and raises the possibility of clinical application in a combination therapy of resveratrol and MED28 suppression in breast cancer cells (44). Another recent study revealed the effects of resveratrol on cyclooxygenase-1 and -2, NF-κB, MMP-9 and sirtuin 1 mRNA expression in the hearts of streptozotocin-induced diabetic rats (45).…”

Anti-tumor effects and cellular mechanisms of resveratrol

“…A subunit of the mammalian mediator complex for transcription called MED28, the overexpression of which could increase migration, was also reduced by resveratrol through the EGFR/ PI3K signaling pathway (72). The in vivo research of breast cancer also confirmed the effect of inhibition of MMP-9 in the anti-metastasis process.…”

Chemically-Induced DNA Damage, Mutagenesis, and Cancer

“…It has been suggested that resveratrol plays a role in inhibiting the expression of MMP (mainly MMP-9) [174][175][176][177] and angiogenesis markers such as VEGF, EGFR or FGF-2 [79,178]. Resveratrol reduced the phorbo-12-myristate 13-acetate (PMA)-induced migration and invasion ability of liver cancer HepG2 and Hep3B cells.…”