Abstract
It is well established that retinoids are essential to maintain normal proliferation and differentiation of cells and tissues, and that impaired retinoid metabolism is profoundly involved in the carcinogenesis of various organs. In hepatocarcinogenesis, localized retinoid deficiency as well as appearances of cellular retinoic acid-binding protein and cellular retinoid-binding protein, F-type of type III, in tumor tissue are characteristic. We found a novel synthetic "acyclic retinoid" which binds to CRABP. The acyclic retinoid inhibited experimental hepatomas in mice and rats, and reduced the growth rate of human hepatoma-derived cell lines. Furthermore, the acyclic retinoid down-regulated the alpha-fetoprotein mRNA expression and up-regulated the albumin mRNA. The acyclic retinoid is supposed to exert its action by, at first, binding to nuclear retinoid receptors such as RARβ, although further mechanisms are now under investigation. Prevention of the post-resection reccurence of hepatoma (hepatocarcinogenesis) is progressing in the phase II clinical trial. In addition, treatment of acute promyelocytic leukemia with retinoic acid is also described.
