Cancer chemopreventive activity of brassinin, a phytoalexin from cabbage
| Autor: | Mehta, R. G., Liu, J., Constantinou, Andreas I., Thomas, C. F., Hawthorne, M., You, M., Gerhäuser, C., Pezzuto, J. M., Moon, R. C., Moriarty, R. M. |
|---|---|
| Přispěvatelé: | Constantinou, Andreas I. [0000-0003-0365-1821] |
| Rok vydání: | 1995 |
| Předmět: |
Male
Cancer Research Skin Neoplasms Indoles cyclization skin tumor cancer inhibition DMBA medicine.disease_cause Support U.S. Gov't P.H.S Mice vegetable protein Anticarcinogen antineoplastic agent chemistry.chemical_classification Mice Inbred BALB C cancer prevention Cruciferous vegetables Phytoalexin article Biological activity General Medicine unclassified drug 7 12 dimethylbenz[a]anthracene female Biochemistry priority journal Female brassinin precancer 9 10-Dimethyl-1 2-benzanthracene Brassica animal tissue phorbol 13 acetate 12 myristate organ culture Organ Culture Techniques drug activity male Thiocarbamates medicine Animals Anticarcinogenic Agents controlled study Support Non-U.S. Gov't indole derivative mouse breast Indole test structure activity relation nonhuman Animal skin carcinogenesis breast carcinogenesis tumor promotion chemoprophylaxis Mammary Neoplasms Experimental drug activation drug metabolism drug structure chemistry Cell culture drug synthesis Carcinogenesis |
| Zdroj: | Carcinogenesis |
| Popis: | Brassinin [3-(S-methyldithiocarbamoyl aminomethyl indole], a phytoalexin first identified as a constituent of cabbage, was synthesized and evaluated for cancer chemopreventive activity. Dose-dependent inhibition of 7,12-dimethylbenz [a]anthracene (DMBA)-induced preneoplastic lesion formation was observed with mouse mammary glands in organ culture, as was dose-dependent inhibition of DMBA-induced mouse skin tumors that were promoted by treatment with 12-O-tetradecanoylphorbol-13-acetate. Cyclobrassinin is a biologically derived product of the oxidative cyclization of brassinin, and was as active as the parent compound in inhibiting the formation of preneoplastic mammary lesions in culture however, 2-methyibrassinin was not significantly active in this process. Therefore, oxidative cyclization may be an effective metabolic activation step. As judged by these tumor inhibition studies in conjunction with potential to induce phase II enzymes in mice or cell culture, brassinin may be effective as a chemopreventive agent during both the initiation and promotion phases of carcinogenesis. This is the first report documenting the chemopreventive potential of structurally novel indole-based phytoalexins that are naturally occurring in cruciferous vegetables, and the synthetic route described herein has proven amenable for scale-up production. The bifunctional structural nature of brassinin, bearing both an indole nucleus and a dithiocarbamoyl-aminomethyl moiety, is notably similar to the individual structural elements of other known chemopreventive agents such as indole-3-carbinol or benzylisothiocyanate. The favorable biological activity demonstrated by the compound may originate from the presence of these two moieties. © 1995 Oxford University Press. 16 399 404 Cited By :175 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|