Antitumor activity of vitamin A and its derivatives.

ABSTRACT

Studies were conducted for investigation of the inhibitory effect on the development of experimental tumors of the skin and liver with vitamin A-like compounds, with a particular focus on a new synthetic derivative of the polyprenoic acid 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E-5166). Incidence of skin papilloma, chemically induced in mice, was significantly influenced by dietary vitamin A contents. When given orally at a dose of 200 mg/kg body weight, beta-carotene regressed the skin papilloma to some extent (-16% at 14 days), although its effect was much weaker than that of E-5166 (-43%). E-5166 also significantly reduced tumor incidences of experimental hepatomas induced by chemical carcinogen in rats as well as in "spontaneous" hepatoma-bearing mice (C3H/HeNCrj) genetically determined. Further chemical studies revealed that retinol was locally deficient in the hepatomas but not in adjacent normal livers In particular, anhydroretinol was newly detected in the tumors of spontaneous hepatoma-bearing mice, suggesting increased conversion of retinol into the inactive metabolite. Moreover, cellular retinoid-binding protein, F-type (an oncofetal protein), also newly appeared exclusively in the hepatoma tissues, suggesting that the preventive effect of E-5166 on hepatocarcinogenesis was mediated, at least in part, through its binding with the new retinoid receptor.