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.
Breast cancer is a systemic malignant disease that is a major cause of cancer-related death among women worldwide. Recently, multiple lines of evidence from epidemiologic studies have suggested that epigenetic and genetic changes are involved in breast cancer development. In breast cancer patients, hormone receptor status, breast cancer stem-like cell population, and tumor microenvironment are reflective of breast cancer progression, drug resistance, and tumor recurrence. Strong relationships between a phytochemical-rich diet and a reversal of epigenetic alterations and/or modulated signaling pathways of carcinogenesis (initiation, promotion, and progression) suggest a potential approach for preventing breast cancer. Additionally, dietary consumption of natural phenolic compounds containing phytoestrogen properties exerts beneficial effects in breast cancer chemoprevention. In this review, we summarize the specific chemopreventive targets of representative phenolic compounds with an emphasis on their efficacy at interfering with epigenetic event related hormonal and nonhormonal signaling cascades that are responsible for multistage breast carcinogenesis.
Nobiletin (NOB) and 5-demethylnobiletin (DMNB) are unique polymethoxyflavones (PMFs) found in citrus peel that exhibit anti-tumoral action in several cancer cell models. The differences between NOB and DMNB with respect to their anti-proliferative potencies and underlying molecular mechanism were compared in this contribution. The results of the cell viability assay suggested that DMNB resulted in more enhanced growth inhibitory effects than NOB in human colon cancer cell lines (HCT-116, HT-29 and COLO 205). Flow cytometry data found that DMNB inhibited proliferation in COLO 205 cells by predominantly inducing apoptosis. A xenograft mouse model further demonstrated that DMNB exhibited more preferential anti-colon cancer effects than NOB via its ability to induce p53-regulated cell death signaling (apoptosis and autophagy) and inhibit key cellular markers associated with inflammation and angiogenesis. Taken together, our findings provide evidence for the first time that natural bioactive DMNB might serve as a promising polymethoxyflavone for chemoprevention of colorectal cancer.
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