alpha-carotene and Cell-Transformation--Neoplastic

High intakes of carotenoid-rich fruits and vegetables are associated with a reduced risk of various cancers including colon cancer. A human intervention study with carrot and tomato juice should show whether a diet rich in carotenoids, especially high in beta-carotene and lycopene, can modify luminal processes relevant to colon carcinogenesis. In a randomised cross-over trial, twenty-two healthy young men on a low-carotenoid diet consumed 330 ml tomato or carrot juice per d for 2 weeks. Intervention periods were preceded by 2-week depletion phases. At the end of each study period, faeces of twelve volunteers were collected for chemical analyses and use in cell-culture systems. Consumption of carrot juice led to a marked increase of beta-carotene and alpha-carotene in faeces and faecal water, as did lycopene after consumption of tomato juice. In the succeeding depletion phases, carotenoid contents in faeces and faecal water returned to their initial values. Faecal water showed high dose-dependent cytotoxic and anti-proliferative effects on colon adenocarcinoma cells (HT29). These effects were not markedly changed by carrot and tomato juice consumption. Neither bile acid concentrations nor activities of the bacterial enzymes beta-glucosidase and beta-glucuronidase in faecal water changed after carrot and tomato juice consumption. Faecal water pH decreased only after carrot juice consumption. SCFA were probably not responsible for this effect, as SCFA concentrations and profiles did not change significantly. In summary, in the present study, 2-week interventions with carotenoid-rich juices led only to minor changes in investigated luminal biomarkers relevant to colon carcinogenesis.

Topics: Adult; beta Carotene; Beverages; Biomarkers, Tumor; Carotenoids; Cell Death; Cell Proliferation; Cell Transformation, Neoplastic; Colonic Neoplasms; Cross-Over Studies; Daucus carota; Feces; Humans; Lycopene; Male; Solanum lycopersicum; Tumor Cells, Cultured; Water

We have previously demonstrated that diverse carotenoids inhibit chemically induced neoplastic transformation in 10T1/2 cells. To address their mechanism of action, the effects of six diverse carotenoids, with or without provitamin A activity, on gap junctional communication and lipid peroxidation have been investigated. beta-Carotene, canthaxanthin, lutein, lycopene and alpha-carotene increased gap junctional intercellular communication in a dose-dependent manner in the above order of potency, whereas m-bixin was inactive at concentrations up to 10(-5) M. alpha-Tocopherol, a potent chain-breaking antioxidant, caused a marginal enhancement of junctional communication. The enhancement of junctional communication by diverse carotenoids showed a strong statistical correlation with their previously determined ability to inhibit methylcholanthrene-induced neoplastic transformation (r = -0.75). All carotenoids tested inhibited lipid peroxidation, but with differing potencies. alpha-Tocopherol was the most active inhibitor followed by m-bixin. The capacity of carotenoids or alpha-tocopherol to inhibit lipid peroxidation was neither consistent with their ability to inhibit neoplastic transformation (r = 0.30) nor to increase junctional communication (r = 0.12). Since junctional communication appears to play an important role in cell growth control and carcinogenesis, we propose that in this system carotenoid-enhanced intercellular communication provides a mechanistic basis for the cancer chemopreventive action of carotenoids. These data also imply that carotenoids function in a manner analogous to retinoids in the 10T1/2 assay system. Interestingly this activity appears independent of their provitamin A status.

Topics: Animals; beta Carotene; Canthaxanthin; Carotenoids; Cell Communication; Cell Transformation, Neoplastic; Lipid Peroxidation; Lutein; Lycopene; Mice; Vitamin E