INHIBITION OF HELA-CELL PROLIFERATION BY 4-HYDROXYNONENAL IS ASSOCIATED WITH ENHANCED EXPRESSION OF THE C-FOS ONCOGENE

Previous studies have shown that the highly reactive aldehyde 4-hydrox ynonenal (HNE), a mediator of oxidative stress, can either stimulate o r inhibit cell proliferation, depending on the concentration of the al dehyde and the presence of serum. HNE can also induce differentiation of tumour cells in vitro and inhibit the tumour development in vivo. T he aim of the study presented was to find out more details about the b asic mechanisms by which HNE influences cell growth behaviour Therefor e we analysed the effect of HNE on the transcription of the c-fos gene in HeLa cells, to clarify the pathway by which the aldehyde modulates gene transcription and growth behaviour of the cells. At a supraphysi ological concentration (50 mu M) the aldehyde caused an enhanced c-fos transcription (as measured by the reverse transcriptase/polymerase ch ain reaction assay), while it inhibited cell proliferation markedly Th erefore, we assume that among the ''early'' effects of HNE on cellular growth regulation might be an altered expression of the ''early respo nse'' genes (c-fos), while a ''late'' effect might be an altered autoc rine/paracrine growth regulation of the cells. This finding on the pos sible basic mechanisms of the biological effects of HNE together with the already described high toxicity of the aldehyde for cancer cells g ive support for the further evaluation of the possible use of HNE in c ancer biotherapy.