Abstract
We have found that synthetic geranylgeranoic acid (GGA), 4, 5-didehydro GGA and 2, 3-dihydro GGA all equally bind to cellular retinoic acid-binding protein. Furthermore GGA and 4, 5-didehydro GGA were demonstrated as potent ligands both for nuclear retionic acid receptor and retinoid X receptor so that we named these polyprenoic acids as "acyclic retinoids". Recently, phase II clinical trial clearly showed efficacy of acyclic retinoid (4, 5-didehydro GGA) to prevent second primary hepatoma after surgical resection of the original tumor or the percutaneous injection of ethanol. A molecular mechanism underlying hepatoma preventive action is discussed with a special reference to apoptosis from animal and cell biological experiments. We speculate that GGA may be an endogenous signaling molecule which is synthesized de novo from mevalonate pathway.
