| pubmed-article:1902075 | pubmed:abstractText | Oxysterols, a family of naturally occurring products, have been shown to possess several biological activities. In particular, they are more toxic towards tumor cells than towards normal cells. In addition, they markedly modify immune cell responses. To carry out in vivo studies, we have synthesized phosphodiesters of 7 beta-hydroxycholesterol (JB69 and XA29). These water-soluble prodrugs have a similar toxicity to their parent compound under in vitro conditions. When administered intraperitoneally to mice bearing the P815 mastocytoma, they induced significant increases in life span. The results depend on the administration protocol. Under appropriate conditions, 20 to 40% of treated mice recover completely. This, together with their immunological effect, suggests that these oxysterols should be considered to be agents for immunochemotherapeutic investigations. By their ability to inhibit HMG CoA reductase, they may prevent the biosynthesis of prenyl groups whose coupling to oncogenes is responsible for the biological activity expression of the latter. Several indications are compatible with an effect on the cell membrane. Our recent studies have shown Protein Kinase C to be a target of oxysterols. On the basis of results obtained by our group and by others, we believe that oxysterols may form a new class of antitumor agents. | lld:pubmed |
