engleski

4-Hydroxy-2-nonenal may be important regulator of the growth control of osteosarcoma cells: human osteosarcoma cultures with different sensitivity to HNE

4-Hydroxy-2-nonenal (HNE) is a major aldehydic product of lipid peroxidation known to exert several biological and cytotoxic effects. When used in high concentrations, HNE can cause cell death ; but in lower concentrations, it can influence cell proliferation and differentiation. It is known that cells of different origin have different sensitivity to HNE. In our experiments we have used human osteosarcoma cells (HOS) of the same origin, but with different degree of differentiation. Cells were different with respect to number of mytosis, 3H-thymidine incorporation and number of alkaline phosphatase positive nodules in cell culture. To test influence of HNE on HOS cell proliferation, 3H-thymidine incorporation assay was used. Results showed that differentiated cultures of HOS cells (cultures with alkaline phosphatase positive nodules) were more sensitive to inhibitory effect of HNE on cell proliferation than undifferentiated. Influence of HNE on HOS cell differentiation was also analyzed. When treated repeatedly with non-cytotoxic concentrations of HNE, decrease in spontaneous cell differentiation measured by formation of alkaline phosphatase positive nodules was observed. To clarify this phenomenon, we measured a content of glutathione (GSH) in these cell lines and found that differentiated HOS cells had less GSH which can explain their higher sensitivity to HNE. Thus, the results obtained indicate that HNE could decrease differentiation of HOS cells, while the process of HOS cells differentiation is associated with changes in cell metabolism resulting in decreased GSH content in those cells. Therefore, HNE might be important regulator of not only proliferation but also differentiation and the overall growth control of malignant mesenchimal cells.

4-hydroxy-2-nonenal; osteosarcoma cells

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