Natural Plants Compounds as Modulators of Epithelial-to-Mesenchymal Transition

Abstract

Epithelial-to-mesenchymal transition (EMT) is a self-regulated physiological process required for tissue repair that, in non-controled conditions may lead to fibrosis, angiogenesis, loss of normal organ function or cancer. Although several molecular pathways involved in EMT regulation have been described, this process does not have any specific treatment. This article introduces a systematic review of effective natural plant compounds and their extract that modulates the pathological EMT or its deleterious effects, through acting on different cellular signal transduction pathways both in vivo and in vitro . Thereby, cryptotanshinone, resveratrol, oxymatrine, ligustrazine, osthole, codonolactone, betanin, tannic acid, gentiopicroside, curcumin, genistein, paeoniflorin, gambogic acid and Cinnamomum cassia extracts inhibit EMT acting on transforming growth factor-β (TGF-β)/Smads signaling pathways. Gedunin, carnosol, celastrol, black rice anthocyanins, Duchesnea indica , cordycepin and Celastrus orbiculatus extract downregulate vimectin, fibronectin and N-cadherin. Sulforaphane, luteolin, celastrol, curcumin, arctigenin inhibit β-catenin signaling pathways. Salvianolic acid-A and plumbagin block oxidative stress, while honokiol, gallic acid, piperlongumine, brusatol and paeoniflorin inhibit EMT transcription factors such as SNAIL, TWIST and ZEB. Plectranthoic acid, resveratrol, genistein, baicalin, polyphyllin I, cairicoside E, luteolin, berberine, nimbolide, curcumin, withaferin-A, jatrophone, ginsenoside-Rb1, honokiol, parthenolide, phoyunnanin-E, epicatechin-3-gallate, gigantol, eupatolide, baicalin and baicalein and nitidine chloride inhibit EMT acting on other signaling pathways (SIRT1, p38 MAPK, NFAT1, SMAD, IL-6, STAT3, AQP5, notch 1, PI3K/Akt, Wnt/β-catenin, NF-κB, FAK/AKT, Hh). Despite the huge amount of preclinical data regarding EMT modulation by the natural compounds of plant, clinical translation is poor. Additionally, this review highlights some relevant examples of clinical trials using natural plant compounds to modulate EMT and its deleterious effects. Overall, this opens up new therapeutic alternatives in cancer, inflammatory and fibrosing diseases through the control of EMT process.

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

“…It has been reported that NPCs exhibit anticancer, anti-inflammatory and anti-fibrotic effects, which inhibits pathological EMT through different cell signal transduction pathways (10). In the present study, the expression of epithelial marker E-cadherin increased following CVB-D treatment, while the mesenchymal markers N-cadherin and vimentin decreased.…”

“…In addition, bioactive natural components extracted from plants have received attention for their inhibition of epithelial-mesenchymal transformation (EMT) through anti-inflammatory, anti-fibrosis or anti-oxidant mechanisms (9). It has been demonstrated that pathological EMT is inhibited by NPCs via different cellular signal transduction pathways (10).…”

Citrus Flavones: An Update on Sources, Biological Functions, and Health Promoting Properties

“…Luteolin was extensively used as anticancer molecule in different studies and its efficiency was demonstrated both in vitro and in vivo. Considering different typologies of cancer, it is able to reduce the tumor size, growth rate, and vascularization, as described by Ahmed et al [116], Imran et al [117], and Avila-Carrasco et al [118] in recent reviews, mainly by a mechanism in which apoptosis of cancer cells is induced.…”

Iron and copper complexes with antioxidant activity as inhibitors of the metastatic potential of glioma cells

“…14 Namely, during EMT, cancer cells undergo a series of changes (biochemical, morphologic and genetic) that allow them to have a more mesenchymal-like phenotype that is thought to be necessary to promote cancer cell migration and invasion, and their escape from the primary tumor. 14 Despite the fact that the search for compounds able to interfere with the EMT process has been increasing in the past years, it is still mainly based in the use of natural compounds isolated from plants, 15 while the use of metal-based compounds in this branch of medicinal chemistry remains poorly researched. In addition to targeting EMT, several of these metalbased compounds also aim to affect Reactive Oxygen Species (ROS) equilibrium 8,11,12,16 since ROS can act as signaling molecules in many cellular pathways, including those involved in tumor progression.…”