Cytotoxic and apoptotic effects of single and mixed oxides of beta-sitosterol on HepG2-cells.

While health implications caused by cholesterol oxidation products (COPs) seem to be generally accepted, research on phytosterol oxidation products (POPs) is still limited. Since POPs are commercially not available knowledge on their toxic activities is mainly derived from blends instead of pure compounds. Therefore the aim of the present study was to examine the cytotoxicity of three individual oxidation products of beta-sitosterol, 7-ketositosterol, 7beta-OH-sitosterol, 7alpha-OH-sitosterol, a mixture of 6beta-OH-3-keto-sitosterol/6alpha-OH-3-keto-sitosterol (ratio 4:3) and a mixture of polar oxides towards HepG2-cells. All tested compounds were found to reduce cell viability in a significant and concentration dependent way, particularly 7-keto- and 7alpha-OH-sitosterol showed to be highly active. Only for 7-ketositosterol an increase in early apoptotic cells was observed. Enhancement of O(2)(-) production was assessed for all oxides, whereas malondialdehyd (MDA) levels were increased by 7-keto- and 7alpha-OH-sitosterol only. However, cell death did not appear to be necessarily dependent on the generation of oxidative stress. Further no DNA strand breaks were observed with the COMET assay. By assessing the accumulation of single oxidation products in the cells a link between higher proportions of oxides inside the cells and their cytotoxic potential could be found.