Cytotoxic properties of a phosphoglycoconjugated derivative of 7 beta-hydroxycholesterol upon normal and tumor cells in culture.
Ключови думи
Резюме
The cytotoxic activity of a new hydrosoluble axysterol derivative, a phosphoric acid diester of 7 beta-hydroxycholesterol (7 beta-OHC, one of the most toxic oxysterol) and of galactose has been evaluated using cultured tumor cells of various origins, and compared with 7 beta-OHC. As its parent compound, XG-142 exhibits a significant cytotoxic activity against all the cell lines tested, but the IC50's were higher than those obtained with 7 beta-OHC. Moreover, the cytotoxicity was slower to appear than after a 7 beta-OHC treatment. Cell phase distribution was analysed, and revealed some differences between the two compounds. Both oxysterols induced apoptosis at micromolar concentrations, as evidenced by several methods including agarose gel electrophoresis of fragmented DNA and flow cytometry of propidium iodide labeled cells. Apoptosis was also obtained when 7 beta-OHC and XG-142 were combined at concentrations unable to induce this type of cell death when used separately. Upon normal murine spleen cells, XG-142 was found to be less toxic than 7 beta-OHC, and the capacity to respond to Con A stimulation was preserved. Therefore, XG-142 can be considered as a promising soluble analogue of 7 beta-OHC, and its application as anticancer agent should be considered.