Vaccinium angustifolium (lowbush blueberry) leaf extract increases extravillous trophoblast cell migration and invasion in vitro

Abstract

Perturbations to extravillous trophoblast (EVT) cell migration and invasion are associated with the development of placenta-mediated diseases. Phytochemicals found in the lowbush blueberry plant (Vaccinium angustifolium) have been shown to influence cell migration and invasion in models of tumorigenesis and noncancerous, healthy cells, however never in EVT cells. We hypothesized that the phenolic compounds present in V. angustifolium leaf extract promote trophoblast migration and invasion. Using the HTR-8/SVneo human EVT cell line and Boyden chamber assays, the influence of V. angustifolium leaf extract (0 to 2 × 10 ng/ml) on trophoblast cell migration (n = 4) and invasion (n = 4) was determined. Cellular proliferation and viability were assessed using immunoreactivity to Ki67 (n = 3) and trypan blue exclusion assays (n = 3), respectively. At 20 ng/ml, V. angustifolium leaf extract increased HTR-8/SVneo cell migration and invasion (p < .01) and did not affect cell proliferation or viability. Chlorogenic acid was identified as a major phenolic compound of the leaf extract and the most active compound. Evidence from Western blot analysis (n = 3) suggests that the effects of the leaf extract and chlorogenic acid on trophoblast migration and invasion are mediated through an adenosine monophosphate-activated protein (AMP) kinase-dependent mechanism. Further investigations examining the potential therapeutic applications of this natural health product extract and its major chemical compounds in the context of placenta-mediated diseases are warranted.

Watermelon‐Derived Extracellular Vesicles Influence Human Ex Vivo Placental Cell Behavior by Altering Intestinal Secretions

“…[ 25 ] Currently, there are no reliable markers for plant‐derived EVs, [ 26 ] however comparison (Table S2 , Supporting Information) of the WMEV proteome with published data on EV‐like particles isolated from other plant species [ 27 , 28 , 29 , 30 ] revealed common proteins, including S adenosylhomocysteine, that are postulated to be candidate markers of plant EVs. [ 26 ] Moreover, proteomic data suggest that as well as multivesicular bodies (MVBs), which are the source of the exosome EV subtype in animals, plant EVs originate from additional organelles; analyses of the protein (Figures 1d ) and DNA (Figure 1e,f ) implicate plastids.…”

“…Further, WMEVs were not contaminated with proteins usually found in other cellular compartments, miRNA presence was not dependent on sequence and the levels of enriched miRNAs and their predicted protein targets were inversely correlated (Figure S1e, Supporting Information), suggesting active cargo sorting, consistent with the findings of other studies. [25] Currently, there are no reliable markers for plant-derived EVs, [26] however comparison (Table S2, Supporting Information) of the WMEV proteome with published data on EV-like particles isolated from other plant species [27][28][29][30] revealed common proteins, including S adenosylhomocysteine, that are postulated to be candidate markers of plant EVs. [26] Moreover, proteomic data suggest that as well as multivesicular bodies (MVBs), which are the source of the exosome EV subtype in animals, plant EVs originate from additional organelles; analyses of the protein (Figures 1d) and Interestingly, 23% of the proteins detected in WMEVs have a human homolog with a sequence identity >50% and coverage >70%.…”

“…[25] Currently, there are no reliable markers for plant-derived EVs, [26] however comparison (Table S2, Supporting Information) of the WMEV proteome with published data on EV-like particles isolated from other plant species [27][28][29][30] revealed common proteins, including S adenosylhomocysteine, that are postulated to be candidate markers of plant EVs. [26] Moreover, proteomic data suggest that as well as multivesicular bodies (MVBs), which are the source of the exosome EV subtype in animals, plant EVs originate from additional organelles; analyses of the protein (Figures 1d) and Interestingly, 23% of the proteins detected in WMEVs have a human homolog with a sequence identity >50% and coverage >70%. Functional enrichment analysis (Figure S2a, Supporting Information) suggests such proteins are involved in human metabolism, gene expression/protein production, and cell death.…”

Cytotoxic, Antimicrobial, Antioxidant Properties and Effects on Cell Migration of Phenolic Compounds of Selected Transylvanian Medicinal Plants

“…On the other hand, the caffeic acid phenethyl ester can stimulate wound re-epithelization and enhance the proliferation of keratinocytes [75]. Ly et al have proved that chlorogenic acid has migration and invasion stimulating effects on trophoblasts through an adenosine monophosphate-activated protein (AMP) kinase-dependent pathway, while not affecting cell proliferation [76]. However, the hydroxybenzoic acids, such as ellagic acid and gallic acid, increase the proliferation and migration of keratinocytes and fibroblasts in a dose-dependent manner [77].…”