Ascorbigen and other indole-derived compounds from Brassica vegetables and their analogs as anticarcinogenic and immunomodulating agents.

Searches for the natural compounds that determine the anticarcinogenic properties of a cruciferous-vegetable diet, revealed the products of alkaloid glucobrassicin biotransformations; among these, ascorbigen, an indole-containing derivative of L-ascorbic acid, was found to be the most abundant. Study of chemical properties of ascorbigen showed that it is capable of different transformations in acidic (including gastric juice) and slightly alkaline (including blood) media. The stable and unstable products of ascorbigen transformation determine the biological properties of the compound. The most important product of ascorbigen transformation in gastric juice is 5,11-dihydroindolo[3,2-b]-carbazole, with a binding affinity to the Ah receptor only 3.7 x 10(-2) lower than that of tetrachlorodibenzodioxin. This compound may be responsible for modifying P450 enzyme activities. Ascorbigen and its analogs are available synthetically. Their biological evaluation showed that some of the compounds of these series are immunomodulators. The most active is N-methylascorbigen, which demonstrates therapeutic effects (inhibition of tumor growth, protection of animals from bacterial and viral infections). The immunomodulatory activity of natural ascorbigen may be an additional factor of importance for the anticarcinogenic properties of a cruciferous-vegetable diet.

[The effect of a clover extract on the proliferation of human and murine lymphocytes in vitro]. / Vliianie ékstrakta klevera na proliferatsiiu limfotsitov cheloveka i myshi in vitro.

The extracts were prepared from meadow clover harvested at the stages of blossoming and budding. The major biological activity of such extracts is represented by flavonoid compounds. The influence of extracts on the proliferation of peripheral blood mononuclear cells obtained from healthy donors and of inbred mouse splenocytes in vitro was analyzed. Both preparations stimulated cellular proliferation. The lever of stimulating activity correlated with the stage-dependent concentration of flavonoids.

[Immunomodulating activity of 1-methyl and 1-ethylascorbigens]. / Izuchenie immunomoduliruiushchei aktivnosti 1-metil- i 1-étilaskorbigenov.

1-Methyl- and 1-ethylascorbigens, derivatives of indole and ascorbic acid are the vitamin C depo-forms with antitumor activity. Relation between the antitumor activity of the derivatives and their immunostimulating action was studied. The derivatives showed similar properties in vitro: they stimulated lymphocyte blast transformation, insignificantly stimulated formation of cytotoxic T-lymphocytes (CTL) in the allogenic mixed culture of lymphocytes (AMLC), inhibited cytotoxicity of natural killer cells (NKC) and had no cytotoxic action in cultures of tumors CaOv and others. In vivo 1-methylascorbigen promoted an increase in the splenocyte count in mice, stimulated 16-fold generation of CTL in AMLC of the splenocytes and retarded the growth of ACATOL tumor in thymus-free mice. 1-Ethylascorbigen had no such effects. The antitumor action of 1-methylascorbigen is likely to be associated with stimulation of CTL generation and not with the increase in the activity of NKC.

[Effect of synthetic beta-carotene on the formation of cytolytic T-lymphocytes]. / Vliianie sinteticheskogo beta-karotina na obrazovanie tsitoliticheskikh T-limfotsitov.

The effect of intraperitoneal injection of beta-carotene in different doses on the formation of cytolytic T lymphocytes (CTL) in a one-way mixed lymphocyte culture (MLC) of allogeneic mice was studied. The maximal cytotoxic activity of lymphocytes was attained in the MLC with splenocytes of mice which received 10 mg/kg beta-carotene 6 days before experimentation. The correlation was studied between the beta-carotene ability to stimulate CTL formation and antineoplastic activity. It was discovered that injection of beta-carotene in doses and times provoking maximal CTL induction had no effect on the animals' lifespan and the size of transplanted sarcoma 180.