Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assessed the anti-mutagenic and anti-promotion properties of two flavones, apigenin and robinetin, and of indole-3-carbinol, because these compounds have been reported in vegetables, the consumption of which has been associated with reduced rates of cancer. However, the active components of these foods and their effects on carcinogenesis have not been established. Anti-mutagenicity was determined in the Salmonella typhimurium assay by measuring the effects of the test compounds on bacterial mutagenesis induced by methyl-nitrosourea (MNU), methyl-n-nitro-N-nitrosoguanidine (MNNG), benzo[a]pyrene (BaP) or 2-aminoanthracene (2-AA). Inclusion of apigenin resulted in a 62% and a 43% inhibition of mutagenicity with 13 nmol of 2-AA and 30 nmol BaP respectively. Robinetin caused an 87% inhibition of mutagenicity by 2-AA, but indole-3-carbinol had little or no effect on the mutagenicity of any of the compounds. None of the three compounds inhibited mutagenesis by MNU or MNNG and none were mutagenic or toxic when tested in the absence of mutagenic compounds at doses up to 20 micrograms/plate. Anti-promotion properties were assessed by measuring the effects of apigenin, robinetin and indole-3-carbinol on induction of ornithine decarboxylase activity (ODC) in mouse epidermis by 17 nmol 12-O-tetradecanoyl phorbol-13-acetate (TPA). Pretreatment of the skin half an hour before TPA with apigenin, robinetin, butylated hydroxyanisole, 13-cis-retinoic acid (all at 50 mumol) or di-fluoromethylornithine (1.6 mumol) inhibited ODC induction at 6 h after TPA by 67-80%. Pretreatment with 50 mumol indole-3-carbinol caused a 78% elevation in the TPA induction at this time. Dose response measurements were conducted with apigenin, indole-3-carbinol and robinetin. Inhibition by 30-90% of TPA-induced ODC was observed at 6 h after TPA in mice pretreated with 12.5-100 mumol apigenin. Pretreatment with 37.5 or 50 mumol indole-3-carbinol or 0.5, 12.5 or 25 mumol robinetin resulted in elevated induction of epidermal ODC by TPA at 6 h after TPA. However, treatment with 50 or 100 mumol robinetin diminished ODC induction at 6 h after TPA. Treatment with 100 mumol apigenin or 50 or 100 mumol indole-3-carbinol in non-TPA-treated mouse skin caused elevations in epidermal ODC. In comparing the time course of ODC induction, indole-3-carbinol (50 mumol) pretreatment shifted the induction of epidermal ODC to earlier times, in addition to elevating ODC induction by TPA.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1986 Jun
PMID:Anti-mutagenesis and anti-promotion by apigenin, robinetin and indole-3-carbinol. 370 57

Ellagic acid, quercetin and robinetin were tested for their ability to antagonize the tumor-initiating activity of benzo[a]pyrene (B[a]P) and (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), the ultimate carcinogenic metabolite of benzo[a]-pyrene. Ellagic acid, robinetin or quercetin (2500 nmol) had no tumor-initiating activity on mouse skin, but the topical application of 2500 nmol of ellagic acid 5 min before a tumor-initiating dose of 200 nmol of B[a]P 7,8-diol-9,10-epoxide-2 caused a 59-66% inhibition in the number of skin tumors per mouse that were observed after 15-20 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate. Similar treatment with 2500 nmol of robinetin or quercetin caused a statistically insignificant 16-24% inhibition in the tumor-initiating activity of 200 nmol of B[a]P 7,8-diol-9,10-epoxide-2 applied 5 min later. Treatment of mice with 2500 nmol of ellagic acid 5 min before the application of 50 nmol of B[a]P inhibited the mean number of skin tumors per mouse by 28-33% after 15-20 weeks of promotion, but these decreases were not statistically significant. Robinetin and quercetin had little or no effect on the tumor-initiating activity of B[a]P on mouse skin. Treatment of preweanling mice with 1/7, 2/7 and 4/7 of the total dose of ellagic acid (300 nmol), robinetin (1400 nmol), myricetin (1400 nmol) or quercetin (1400 nmol) i.p. on their first, eighth and fifteenth day of life, respectively, did not cause the formation of tumors in animals that were killed 9-11 months later. Similar treatment of preweanling mice with the above doses of the phenolic compounds 10 min before the i.p. injection of a total dose of 30 nmol of B[a]P 7,8-diol-9,10-epoxide-2 during the animal's first 15 days of life caused a 44-75% inhibition in the number of diol-epoxide-induced pulmonary tumors per mouse. Similar treatment with these plant phenols had little or no effect on B[a]P-induced pulmonary tumors.
Carcinogenesis 1985 Aug
PMID:Effect of ellagic acid and hydroxylated flavonoids on the tumorigenicity of benzo[a]pyrene and (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene on mouse skin and in the newborn mouse. 392 36