No abstract

No abstract

Although the primary cell cultures from dental pulp and other oral tissue are frequently used to study osteogenic potential and stem cell responses, few systematic and comparative studies on stemness for the dentinogenic differentiation of these cells have been conducted. In the present study, to investigate the stemness of oral primary cells during extended culture, human adult dental pulp cells (hDPCs), periodontal ligament stem cells (hPDLSCs) and gingival fibroblasts (hGFs) were obtained and cultured from pulp tissue, periodontal ligaments, and marginal and attached gingival tissue of extracted third molars, respectively. As shown by fluorescence-activated cell sorting analysis and immunophenotyping, the mesenchymal stem cell markers, CD44, CD73, CD90, CD146 and CD166, were highly expressed in early passage hDPCs, hPDLSCs and hGFs. However, when the cells were treated with osteogenic additives, mineralization markedly increased in the hDPCs and hPDLSCs, but not in the hGFs. Moreover, the expression of dentinogenic markers, such as dentin sialophosphoprotein and dentin matrix protein-1, appeared to decrease during extended culture past passage number 8 of the hDPCs and hPDLSCs. These data suggest that hDPCs and hPDLSCs may have differentiation potential during the early passages, and that their progenitor potential is diminished during extended culture. The hGFs did not show differentiation capability during culture, even though they contained general mesenchymal stem cell surface proteins. The transcriptional expression of dentinogenic markers in hDPCs was not affected by co-culture with hPDLSCs and/or hGFs.

Extracellular acidity has been implicated in enhanced malignancy and metastatic features in various cancer cells. Gastric cancer cell lines (AGS and SNU601) maintained in an acidic medium have increased motility and invasiveness. In this study, we investigated the effect of ellagic acid, a plant-derived phenolic compound, on the acidity-promoted migration and invasion of gastric cancer cells. Treating cells maintained in acidic medium with ellagic acid inhibited acidity-mediated migration and invasion, and reduced the expression of MMP7 and MMP9. Examining regulatory factors contributing to the acidity-mediated invasiveness, we found that an acidic pH increased the expression of COX1 and COX2; importantly, expression decreased under the ellagic acid treatment. The general COX inhibitor, sulindac, also decreased acidity-mediated invasion and expression of MMP7 and MMP9. In addition, acidity increased the mRNA protein expression of transcription factors snail, twist1, and c-myc; these were also reduced by ellagic acid. Together, these results suggest that ellagic acid suppresses acidity-enhanced migration and invasion of gastric cancer cells via inhibition of the expression of multiple factors (COX1, COX2, snail, twist1, and c-myc); for this reason, it may be an effective agent for cancer treatment under acidosis.Nutrients 2019, 11, 3023 2 of 12 to a more mesenchymal-like phenotype [9]. A low-pH environment triggers the loss of E-cadherin expression in melanoma cells, and tumor cells primed at acidic pH have an increased adherence to the surface at normal pH in vitro and a higher metastatic potential in vivo [10,11], implicating the role of acidity in the migration of tumor cells from the original acidic tumor tissue to another non-tumor site. Therefore, treatment of tumors exposed to an acidic environment appears to be an important issue. Considerable attempts have been made to overcome adverse effects caused by acidic environment with strategies such as the use of proton pump inhibitors that block release of cellular proton into extracellular spaces, but the results have not been as successful as expected. Thus, it is imperative to find agents that prevent acidity-mediated malignancy, the activity of which is not inhibited by extracellular acidity.Recently, use of natural medicines has been attracting more attention because of long-established medicinal effects and widely recognized safety. Numerous natural compounds have been extensively examined over the past several decades for their potential in cancer prevention and treatment [12]. Ellagic acid is one of naturally occurring phenolic compounds that has recently received considerable attention due to its diverse pharmacological activities, including antioxidant, anti-inflammatory, and anticancer effects [13]. Ellagic acid is contained in ellagitannins, mainly present in vegetables, nuts, and fruits such as raspberries and pomegranates. Among the various beneficial pharmacological activities of ellagic acid, the capacity to prevent several types of cancers is o...