Various natural carotenoids, besides beta-carotene, were proven to have anticarcinogenic activity, and some of them showed more potent activity than beta-carotene. Thus, these carotenoids (alpha-carotene, lutein, zeaxanthin, lycopene, beta-cryptoxanthin, fucoxanthin, astaxanthin, capsanthin, crocetin and phytoene), as well as beta-carotene, may be useful for cancer prevention. In the case of phytoene, the concept of 'bio-chemoprevention', which means biotechnology-assisted method for cancerchemoprevention, may be applicable. In fact, establishment of mammalian cells producing phytoene was succeeded by the introduction of crtB gene, which encodes phytoene synthase, and these cells were proven to acquire the resistance against carcinogenesis. Antioxidative phytoene-containing animal foods may be classified as a novel type of functional food, which has the preventive activity against carcinogenesis, as well as the ability to reduce the accumulation of oxidative damages, which are hazardous for human health.

Information has been accumulated indicating that diets rich in vegetables and fruits can reduce the risk of a number of chronic diseases, including cancer, cardiovascular disease, diabetes and age-related macular degeneration. Phytochemicals (various factors in plant foods), such as carotenoids, antioxidative vitamins, phenolic compounds, terpenoids, steroids, indoles and fibers, have been considered responsible for the risk reduction. Among them, a mixture of natural carotenoids has been studied extensively and proven to show beneficial effects on human cancer prevention.

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During a cold preservation and reperfusion process of organs, cells are exposed to two major stresses, i.e. changes in oxygen concentration and temperature. c-Jun N-terminal kinase (JNK) /stress-activated protein kinase is activated by various stresses through its phosphorylation. Although hypoxia and subsequent reoxygenation is known to activate JNK, little is known about effects of hypothermia and subsequent rewarming on JNK activation. Thus, we investigated the activation of JNK in human hepatoblastoma (HepG2) cells exposed to a temperature of 5°C and in those rewarmed at 37°C. Western blot analysis using an anti-phospho-JNK antibody revealed that p54 JNK was transiently phosphorylated in cold-stressed cells. In addition, the phosphorylation of p54 JNK was further increased by rewarming of the cells. Since translational and transcriptional abilities were markedly reduced in the cold-stressed cells, effects of translation and transcription inhibitors on the phosphorylation of p54 JNK were determined. Cycloheximide, but not actinomycin D, increased the phosphorylation of p54 JNK in HepG2 cells. These results suggest that hypothermia alone transiently increases the p54 JNK phosphorylation possibly through reduction of protein synthesis and that rewarming after hypothermia stimulates the phosphorylation of p54 JNK.

Insulin increased 2-deoxyglucose (2-DG) uptake via the translocation of glucose transporter (GLUT) 4 to the plasma membrane fraction in rat adipocytes. The stimulatory actions of insulin were accompanied by both an increase in the immunoreactive p85 subunit of phosphatidylinositol (PI) 3-kinase in the plasma membrane fractions and PI 3-kinase activation by tyrosine phosphorylation of the p85 subunit. The ß 3 -adrenoceptor agonist CL316243 (CL) suppressed all the insulin actions in adenosine deaminase (ADA)-treated cells, but was without effect in non-ADA-treated cells. The inhibitory effects of CL on GLUT 4 translocation and PI 3-kinase activation were abolished by the addition of N 6 -phenylisopropyl adenosine. Cholera toxin treatment, which markedly increased intracellular cAMP levels, suppressed increases in the levels of GLUT 4 and PI 3-kinase in the plasma membrane fractions in response to insulin. In addition, dibutyryl (Bt 2 ) cAMP also impaired the activation of PI 3-kinase by insulin. These results indicated that CL suppressed insulin-stimulated glucose transport under conditions where cAMP levels were markedly increased (~ 12-fold). The inhibitory actions of PI 3-kinase activation by insulin were exerted even when cAMP, 8-bromo-cAMP, or Bt2 cAMP was added to immunoprecipitates of the p85 subunit of PI 3-kinase, after treating the cells with insulin. These results suggest that CL suppressed insulin-stimulated PI 3-kinase activity via a cAMPdependent mechanism, at least in part, direct cAMP action in ADA-treated adipocytes, by which PI 3-kinase activation was inhibited, resulting in the decrease in GLUT 4 translocation and subsequent 2-DG uptake in response to insulin.