OXIDIZED CAROTENOIDS, RETINOIDS AND RELATED CONJUGATED POLYENES, AND DERIVED FRACTIONS AND COMPOUNDS USEFUL AS CELL-DIFFERENTIATION INDUCERS, CYTOSTATIC AGENTS, AND ANTI-TUMOR AGENTS.

摘要

'beta'-Carotene, lycopene and canthaxanthin, as representative carotenoids, and to a lesser extent, retinoic acid, a representative retinoid, undergo extensive oxidation to yield substances, insofar as oxidized 'beta'-carotene is a model, which have properties useful as non-toxic agents active against cell proliferation, tumors, and tumorigenic viruses, and useful as promoters of cell differentiation. It is evident from chemical analysis of the highly oxidized 'beta'-carotene product mixture that none of the various forms of vitamin A are present or are present only in minor amounts. Furthermore, the biological activities of oxidized canthaxanthin and lycopene, which cannot form vitamin A, indicate the presence of active substances that are different from vitamin A. Although the cytostatic and differentiation promotion activities of oxidized 'beta'-carotene resemble those of vitamin A itself, generally the effects are more powerful for oxidized 'beta'-carotene in a wide variety of circumstances. Unlike vitamin A, the oxidized 'beta'-carotene of the invention is non-toxic. The oxidized carotenoid is a mixture of compounds which can be divided into a number of fractions according to molecular weight and polarity. The fractions exhibit anticancer activity comparable to, or higher, than the activity of unfractionated oxidized carotenoid.