Related Experiment Videos
Effects of food factors on signal transduction pathways
1The Hormel Institute, University of Minnesota, Austin 55912, USA. zgdong@smig.net
Abstract:
Consumption of plant-derived foods, especially fruits and vegetables, has been linked to decreased risk of cancer. Laboratory studies with animals and cells in culture have shown cancer preventive activity of chemicals isolated from soy, tea, rice and many green, yellow and orange fruits and vegetables. Using cell culture, transgenic mice and knockout mice models to examine the anti-cancer effects of these dietary factors at the molecular level, we found that (11) (-)-epigallocatechin gallate (EGCG), the major active polyphenol in green tea, and theaflavins, the major active components in black tea, inhibit epidermal growth factor (EGF)- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced JB6 cell transformation. At the same dose range that inhibited cell transformation, EGCG and theaflavins inhibited activator protein-1 (AP-1) activation. These compounds also inhibited ultraviolet B (UVB)-induced AP-1 and nuclear factor kappa B (NFkappaB)-dependent transcriptional activation; (2) resveratrol, found at high levels in grapes, inhibited cell transformation through the induction of apoptosis, mediated through JNK and p53-dependent pathways; (3) inositol hexaphosphate (InsP6), an active compound from rice and other grains, inhibited TPA- or EGF-induced transformation and signal transduction through its effects on phosphatidylinositol-3 kinase (PI-3) kinase; (4) phenethyl isothiocyanate (PEITC), which occurs as a conjugate in certain cruciferous vegetables, inhibited cell transformation corresponding with the induction of apoptosis. An elevation of p53 is required for PEITC-induced apoptosis. Our studies indicated that the chemopreventive effect of these food factors may be mediated by their effects on different signal transduction pathways; (5) retinoids (vitamin A and its metabolites) inhibited tumor promoter-induced cell transformation and tumor promotion in transgenic mice through the inhibition of AP-1 action but not through the activation of retinoic acid response element (RARE).
Insights
Dietary compounds like EGCG from green tea and resveratrol from grapes show cancer-preventive effects by inhibiting cell transformation and activating apoptosis. These natural compounds target key molecular pathways, suggesting a role in cancer chemoprevention.
Area of Science:
- Molecular Biology
- Nutritional Science
- Cancer Research
Background:
- Plant-derived foods, particularly fruits and vegetables, are associated with reduced cancer risk.
- Specific phytochemicals show anti-cancer activity in laboratory settings.
- Understanding the molecular mechanisms of these dietary factors is crucial for chemoprevention.
Purpose of the Study:
- To investigate the anti-cancer effects of specific dietary compounds at the molecular level.
- To examine the impact of these compounds on cell transformation and key signaling pathways.
- To elucidate the mechanisms underlying the chemopreventive potential of food-derived factors.
Main Methods:
- Cell culture studies using JB6 cells.
- Transgenic and knockout mice models.
- Analysis of signal transduction pathways including AP-1, NFkappaB, JNK, p53, and PI-3 kinase.
- Assessment of apoptosis and cell transformation.
Main Results:
- (-)-epigallocatechin gallate (EGCG) and theaflavins inhibited EGF/TPA-induced cell transformation and AP-1 activation.
- Resveratrol induced apoptosis via JNK and p53 pathways, inhibiting cell transformation.
- Inositol hexaphosphate (InsP6) affected PI-3 kinase signaling, inhibiting transformation.
- Phenethyl isothiocyanate (PEITC) induced apoptosis, requiring p53.
- Retinoids inhibited AP-1 action, suppressing tumor promotion.
Conclusions:
- Dietary compounds exert chemopreventive effects by modulating diverse signal transduction pathways.
- Inhibition of cell transformation, induction of apoptosis, and modulation of transcription factors are key mechanisms.
- These findings support the role of specific dietary factors in cancer prevention through molecular targeting.