α‐Mangostin, A Novel Dietary Xanthone, Suppresses TPA‐Mediated MMP‐2 and MMP‐9 Expressions through the ERK Signaling Pathway in MCF‐7 Human Breast Adenocarcinoma Cells

Abstract

This study first investigates the anti-metastatic effect of alpha-mangostin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions in human breast adenocarcinoma cells, MCF-7. First, the result demonstrated alpha-mangostin could inhibit TPA-induced abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and Boyden chamber assay. Data also showed alpha-mangostin could inhibit the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) involved in the downregulation the enzyme activities, protein, and messenger RNA levels of MMP-2 and MMP-9 induced by TPA. Next, alpha-mangostin also strongly inhibited TPA-induced degradation of inhibitor of kappaBalpha (IkappaBalpha) and the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, a dose-dependent inhibition on the binding abilities of NF-kappaB and activator protein-1 (AP-1) by alpha-mangostin treatment was further observed. Further, the treatment of specific inhibitor for ERK (U0126) to MCF-7 cells could inhibit TPA-induced MMP-2 and MMP-9 expressions along with an inhibition on cell invasion and migration. Presented data reveal that alpha-mangostin is a novel, effective, antimetastatic agent that functions by downregulating MMP-2 and MMP-9 gene expressions.

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“…Many studies have revealed α-MGʼs inhibitory activities against invasion and migration of cancer cells, and the inhibition of NF-κB is one of the most important mechanisms for its antimetastatic effects. For example, α-MG exhibited a significant antimetastatic effect against TPA-stimulated human breast cancer MCF-7 cells through the inhibition of nuclear translocation and DNA binding activity of NF-κB via blocking phosphorylation and degradation of IκBα [117]. It has been reported that functions mediated by NF-κB are at least partially performed in cooperation with STAT3.…”

“…Despite showing an improved water solubility, all of them reduced the activity of the parent compound. Aisha et al [138] prepared solid dispersions of α-MG in PVP that showed improved solubility, self-assembly of nanomicelles, and intracellular delivery through endocytosis, ▶ MMP-2/MMP-9 expression↓, ERK1/2↓, IκBα degradation↓, nuclear levels of NF-κB/AP-1↓, NF-κB/AP-1 DNA binding↓ TPA-induced human brest MCF-7 cells [117] pNF-κB/p65Ser552↓, pStat3Ser727↓, pStat3Tyr705↓, MMP9↓, DNA binding activity of NF-κB/Stat3↓, TIMP1 expression↑…”

The Cadin-2-en-1β-ol-1β-D-glucuronopyranoside Suppresses TPA-Mediated Matrix Metalloproteinase-9 Expression Through the ERK Signaling Pathway in MCF-7 Human Breast Adenocarcinoma Cells

“…Breast cancer is the most common female malignancy and the second leading cause of cancer mortality worldwide (1). Invasion and metastasis are fundamental properties of malignant cancer cells and primary factors that promote cancer progression (2,3).…”

“…Invasion and metastasis are fundamental properties of malignant cancer cells and primary factors that promote cancer progression (2,3). The invasion and metastasis of cancer cells involve multistep biological processes and various cytophysiological changes including the degradation of tissue barriers such as the extracellular matrix (ECM) and basement membrane (1,3). ECM degradation and remodeling require the action of proteolytic enzymes, along with matrix metalloproteinases (MMPs) (1,3).…”

“…The invasion and metastasis of cancer cells involve multistep biological processes and various cytophysiological changes including the degradation of tissue barriers such as the extracellular matrix (ECM) and basement membrane (1,3). ECM degradation and remodeling require the action of proteolytic enzymes, along with matrix metalloproteinases (MMPs) (1,3). MMPs are a family of highly homologous zinc-dependent, protein-degrading endopeptidases (4 -6).…”