engleski

The influence of 4-hydroxynonenal on proliferation and differentiation of mesenchimal cells in vitro

We used human osteosarcoma cells (HOS) to test influence of 4-hydroxynonenal (HNE) on cell proliferation and differentiation. HNE caused dose-dependent inhibition of HOS cells proliferation measured by 3H-thymidine incorporation. Repeated treatment with non-cytotoxic concentration of HNE, reduced spontaneous cell differentiation measured by alkaline phosphatase cytochemistry (ALP). Moreover, differentiated cultures of HOS cells (ALP-positive cultures) were more sensitive to inhibitory effect of HNE then undifferentiated HOS cells. Influence of HNE on cell growth in vitro was further analysed on other mesenchimal cell lines (human WI38 fibroblasts and primary culture of normal human osteoblasts). The most resistant cells were human osteoblasts while greatest influence on cell proliferation was noticed on HOS cells. The same was observed when intensity of apoptotic cell death was determined for HNE treated cells. These results indicate that HNE can prevent HOS cells differentiation, reduce their DNA synthesis and induce apoptosis, normal human osteoblasts and WI38 fibroblasts are more resistant on cytotoxic effect of HNE than malignant HOS cells. We suppose that differences in lipid and HNE metabolism between normal and tumor cells might cause observed differential sensitivity to HNE.

4-hydroxynonenal; mesenchimal cells; proliferation; differentiation

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