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Carotenoids and gene regulation
1Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813, USA.
Abstract:
Consumption of dietary carotenoids, plant pigments found in green, yellow, and orange fruits and vegetables, has been linked to decreased risk of cancer. Several intervention trials with beta-carotene, however, have failed to confirm this association. Indeed, in current smokers, beta-carotene appeared to increase risk. These disturbing results have not been explained. Laboratory studies with experimental animals and cells in culture have shown cancer preventive activity for a diverse range of carotenoids. Studies using human and animal cells have identified a gene, connexin 43, whose expression is upregulated by chemopreventive carotenoids and which allows direct intercellular gap junctional communication (GJC). GJC is deficient in many human tumors and its restoration or upregulation is associated with decreased proliferation. This review will focus on the growing body of evidence that carotenoids have unexpected biologic effects in experimental systems, some of which may contribute to their observed cancer preventive properties in models of carcinogenesis.
Insights
Dietary carotenoids, found in colorful produce, may prevent cancer by upregulating connexin 43 and enhancing cell communication (GJC). However, beta-carotene supplements showed mixed results in smokers.
Area of Science:
- Nutritional Biochemistry
- Cancer Chemoprevention
- Molecular Biology
Background:
- Dietary carotenoids are plant pigments associated with reduced cancer risk.
- Intervention trials with beta-carotene have yielded conflicting results, even increasing risk in smokers.
- Carotenoids demonstrate cancer preventive activity in experimental systems.
Purpose of the Study:
- To review evidence on the unexpected biological effects of carotenoids.
- To explore how carotenoids may contribute to cancer prevention.
- To investigate the role of connexin 43 and gap junctional communication (GJC) in carotenoid action.
Main Methods:
- Review of laboratory studies involving experimental animals and cell cultures.
- Analysis of research on gene expression, specifically connexin 43.
- Examination of studies investigating intercellular gap junctional communication (GJC).
Main Results:
- Chemopreventive carotenoids upregulate connexin 43 expression in experimental systems.
- Increased connexin 43 facilitates direct intercellular gap junctional communication (GJC).
- Deficient GJC is observed in many human tumors; its restoration correlates with decreased proliferation.
Conclusions:
- Carotenoids exhibit biological effects beyond simple antioxidant activity.
- Upregulation of connexin 43 and restoration of GJC represent a potential mechanism for carotenoid-mediated cancer prevention.
- Further research is warranted to understand these mechanisms in human carcinogenesis.