Antitumor activity of vitamin A and its derivatives

J Natl Cancer Inst. 1984 Dec;73(6):1389-93.


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.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Antineoplastic Agents*
  • Diet
  • Dose-Response Relationship, Drug
  • Female
  • Liver Neoplasms, Experimental / drug therapy*
  • Methyldimethylaminoazobenzene
  • Mice
  • Mice, Inbred Strains
  • Papilloma / drug therapy*
  • Skin Neoplasms / drug therapy*
  • Structure-Activity Relationship
  • Vitamin A / analogs & derivatives*
  • Vitamin A / therapeutic use*


  • Antineoplastic Agents
  • Vitamin A
  • Methyldimethylaminoazobenzene
  • 9,10-Dimethyl-1,2-benzanthracene