Research suggests that diets high in plant foods are protective of certain types of cancer. Plants are a rich source of antioxidants, and the hypothesis that antioxidants are protective of diseases such as cancer on account of their free radical scavenging activity has gained widespread acceptance. Mechanistically, antioxidants could protect DNA from oxidation, thus decreasing the chance of genetic damage. However, antioxidants from plants, such as flavonoids and other polyphenols, are known to affect cell signalling, which in turn can have a pronounced effect on gene regulation. This regulation can decrease tumour promotion in pre-cancerous cells, effectively switching off tumour promoters and killing the cell through programmed cell death. Evidence suggests that this effect occurs via regulation of the signalling enzyme, protein kinase C (PKC). The antioxidant regulation of PKC has been reviewed by Gopalakrishna and Gundimeda (2002).
Protein kinase C has unique properties that allow it to function as a receptor for both tumour promoters (oxidants such as hydrogen peroxide) and anti-tumour promoters (antioxidants such as polyphenols from plants). Ligands such as diacylglycerol and phorbol esters (tetracyclic diterpenoids in plants) can activate PKC and promote tumorigenesis through the binding to zinc fingers in its regulatory domain. However, PKC can also be activated by oxidants which react with zinc-thiol structures in the zinc fingers of the regulatory domain, causing their collapse and induction of a similar effect to ligand binding. In contrast, the oxidised form of antioxidants (e.g. polyphenolics, curcumin and ellagic acid) and selenium compounds can interact with thiol compounds in a separate catalytic domain and inactivate the signal transduction caused by tumour promoters. Thus, an effective countermeasure to pro-oxidant tumorigenesis is present from antioxidants in plants.
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