ABSTRACT
Marsdeniae tenacissimae extract (MTE), commonly known as Xiao-Ai-Ping in China, is a traditional Chinese herb medicine capable of inhibiting proliferation and metastasis and boosting apoptosis in various cancer cells. However, little is known about the contribution of MTE towards tumor angiogenesis and the underlying mechanism. The present study aimed to evaluate the effects of MTE on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) and the molecular mechanism. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS) and PI-stained flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of HUVECs by arresting cell cycle at S phase (P < 0.05). Annexin V-FITC/PI-stained flow cytometry confirmed that MTE (160 μL·L) enhanced the apoptosis of HUVECs significantly (P < 0.001). Real-time quantitative RT-PCR and Western blot analyses showed an increase in Bax expression and a sharply decline in Bcl-2 expression; caspase-3 was activated simultaneously in a dose-dependent manner (P < 0.05). Further study observed the dose-dependent down-regulation of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2), P2Y6 receptor (P2Y6R), and chemokine (C-C motif) ligand 2 (CCL-2), along with the activation of PKC Δ and up-regulation of p53 in a dose-dependent manner in MTE-treated selected cells (P < 0.05). Collectively, the results from the present study suggested that MTE suppressed the proliferation by attenuating CCL-2-mediated VEGF/VEGFR2 interactions and promoted the apoptosis through PKCΔ-induced p53-dependent mitochondrial pathway in HUVECs, supporting that MTE may be developed as a potent anti-cancer medicine.
Subject(s)
Humans , Apoptosis , Cell Cycle , Cell Proliferation , Human Umbilical Vein Endothelial Cells , Cell Biology , Metabolism , Marsdenia , Chemistry , Plant Extracts , Pharmacology , Protein Kinase C , Genetics , Metabolism , Signal Transduction , Vascular Endothelial Growth Factor A , Genetics , Metabolism , Vascular Endothelial Growth Factor Receptor-2 , Genetics , MetabolismABSTRACT
OBJECTIVE@#To invest the differences among mesenchymal stem cells (MSCs) derived from different tissues and their impacts on clinical applications.@*METHODS@#In this study, MSCs were isolated from adipose tissue (AD), umbilical cord tissue (UC), and menstrual blood (Men) and compared their biological characteristics in terms of proliferation capacity, passage capacity, colony formation, and surface markers were compared.@*RESULTS@#The stem cells (SCs) obtained from different sources were all characterized as MSCs, but demonstrated some differences. Umbilical cord-derived MSCs (UCMSCs) were able to overcome density inhibition. The proliferation rate decreased in the order UCMSCs > MenSCs > ADSCs, while the colony-forming ability decreased in the order MenSCs > ADSCs > UCMSCs. Based on gene-expression data for MSCs from different sources within the same donor, 768 MenSC genes were found that were specifically upregulated or downregulated compared with bone marrow-derived MSCs and UCMSCs, most of which were involved in cell function-related pathways. In addition, MenSCs appeared to be superior in terms of immune inflammation, stress response, and neural differentiation potentials, but weaker in terms of osteogenic and chondrogenic differentiation capacities, compared with UCMSCs and bone marrow-derived MSCs.@*CONCLUSIONS@#MenSCs have higher extraction efficiency, colony-forming ability, and long time passage capacity. Although the proliferation capacity is inferior to UCMSCs.
ABSTRACT
Objective: To invest the differences among mesenchymal stem cells (MSCs) derived from different tissues and their impacts on clinical applications. Methods: In this study, MSCs were isolated from adipose tissue (AD), umbilical cord tissue (UC), and menstrual blood (Men) and compared their biological characteristics in terms of proliferation capacity, passage capacity, colony formation, and surface markers were compared. Results: The stem cells (SCs) obtained from different sources were all characterized as MSCs, but demonstrated some differences. Umbilical cord-derived MSCs (UCMSCs) were able to overcome density inhibition. The proliferation rate decreased in the order UCMSCs > MenSCs > ADSCs, while the colony-forming ability decreased in the order MenSCs > ADSCs > UCMSCs. Based on gene-expression data for MSCs from different sources within the same donor, 768 MenSC genes were found that were specifically upregulated or downregulated compared with bone marrow-derived MSCs and UCMSCs, most of which were involved in cell function-related pathways. In addition, MenSCs appeared to be superior in terms of immune inflammation, stress response, and neural differentiation potentials, but weaker in terms of osteogenic and chondrogenic differentiation capacities, compared with UCMSCs and bone marrow-derived MSCs. Conclusions: MenSCs have higher extraction efficiency, colony-forming ability, and long time passage capacity. Although the proliferation capacity is inferior to UCMSCs.