RESUMEN
Glioblastoma is the most aggressive type of brain tumor, with current therapies failing to significantly improve patient survival. Vitamins have important effects on cellular processes that are relevant for tumor development and progression. AIM: The present study explored the effect of pyridoxine or cobalamin supplementation on the viability and cell cycle progression of human glioblastoma cell line U-87 MG. METHOD: Cell cultures were treated with increasing concentrations of pyridoxine or cobalamin for 24-72 h. After supplementation, cell viability and cell cycle progression were assessed by spectrophotometry and flow cytometry. Analysis of Bcl-2 and active caspase 3 expression in supplemented cells was performed by western blot. RESULT: The results show that pyridoxine supplementation decreases cell viability in a dose and time dependent manner. Loss of viability in pyridoxin-supplemented cells is probably related to less cell cycle progression, higher active caspase 3 expression and apoptosis. In addition, Bcl-2 expression did not appear to be altered by vitamin supplementation, but active caspase 3 expression was significantly increased in pyridoxine-, but not cobalamin-supplemented cells, furthermore, cobalamin inhibited the pyridoxine cytotoxicity in the cell viability assay when combined. CONCLUSION: The results suggest that pyridoxine supplementation promotes apoptosis in human glioblastoma-derived cells and may be useful to enhance the effect of cytotoxic therapies in vivo.
RESUMEN
The process by which blood cells are generated has been widely studied in homeostasis and during pathogen-triggered inflammatory response. Recently, murine lungs have been shown to be a significant source of hematopoietic progenitors in a process known as extramedullary hematopoiesis. Using multiparametric flow cytometry, we have identified mesenchymal, endothelial, and hematopoietic progenitor cells that express the secreted small protein Isthmin 1 (ISM1). Further characterization of hematopoietic progenitor cells indicated that ISM1+ Lineage- Sca-1+ c-kit+ (ISM1+ LSK) cells are enriched in short-term hematopoietic stem cells (ST-HSCs). Moreover, most Sca-1+ ISM1+ cells express the residence marker CD49a, and this correlated with their localization in the extravascular region of the lung, indicating that ISM1+ cells are lung-resident cells. We also observed that ISM1+ cells express TLR4, TLR5, and TLR9, and, in a mouse model of sepsis induced by P. aeruginosa, we observed that all the LSK and ISM1+LSK cells were affected. We conclude that ISM1 is a novel biomarker associated with progenitor-like cells. ISM1+ cells are involved in the response to a bacterial challenge, suggesting an association between ISM1-producing cells and dangerous inflammatory responses like sepsis.
