Mechanisms by which natural polyphenols regulate the expression of cytoprotective genes
type: CreativeWork
description: Epidemiological studies have shown that a diet high in fruit and vegetables has an inverse association with the occurrence of various degenerative diseases such as cancer, cardiovascular disease, neuro-degenerative disease and diabetes. Clinical and animal studies using fruit and vegetable extracts have shown that polyphenols abundant in plants may account for the beneficial effect of diets high in fruit and vegetables. Following these findings, laboratories worldwide are investigating the mechanisms underlying the health effects exerted by polyphenols. Although many studies have investigated the effect of various polyphenols on cancer cells, such as inhibition of cell growth, induction of apoptosis, tumorigenesis, few studies have been carried out to examine their effect on normal cells and whether they could prevent the initiation of cancer. DNA damage, one of the early steps in the tumorigenic process, may be caused by toxicants and oxidative stress either from the environment or from endogenous sources. Therefore, to prevent such damage, multiple mechanisms are deployed by cells to combat the toxic insult and reduce oxidative stress. The CNC-bZIP transcription factor, Nrf2, is known to regulate the expression of many of the genes involved in these processes. Under homeostatic conditions, the Nrf2 protein is targeted by its inhibitor Keap1 for ubiquitination in the cytosol. Upon redox stress, induced by low molecular weight electrophiles, Nrf2 can evade ubiquitination and translocate into the nucleus, where it heterodimerizes with members of the small Maf family of transcription factors and bind to the antioxidant response element (ARE) in the promoter region of many cellular defence genes, leading to the up-regulation of their transcription. In our study, we examined whether polyphenols could affect the Nrf2-ARE signalling pathway. Preliminary screening was first carried out using AREc32 cells to find flavonoids which have ARE-inducing ability. Flavonoids, which…
abstract: Epidemiological studies have shown that a diet high in fruit and vegetables has an inverse association with the occurrence of various degenerative diseases such as cancer, cardiovascular disease, neuro-degenerative disease and diabetes. Clinical and animal studies using fruit and vegetable extracts have shown that polyphenols abundant in plants may account for the beneficial effect of diets high in fruit and vegetables. Following these findings, laboratories worldwide are investigating the mechanisms underlying the health effects exerted by polyphenols. Although many studies have investigated the effect of various polyphenols on cancer cells, such as inhibition of cell growth, induction of apoptosis, tumorigenesis, few studies have been carried out to examine their effect on normal cells and whether they could prevent the initiation of cancer. DNA damage, one of the early steps in the tumorigenic process, may be caused by toxicants and oxidative stress either from the environment or from endogenous sources. Therefore, to prevent such damage, multiple mechanisms are deployed by cells to combat the toxic insult and reduce oxidative stress. The CNC-bZIP transcription factor, Nrf2, is known to regulate the expression of many of the genes involved in these processes. Under homeostatic conditions, the Nrf2 protein is targeted by its inhibitor Keap1 for ubiquitination in the cytosol. Upon redox stress, induced by low molecular weight electrophiles, Nrf2 can evade ubiquitination and translocate into the nucleus, where it heterodimerizes with members of the small Maf family of transcription factors and bind to the antioxidant response element (ARE) in the promoter region of many cellular defence genes, leading to the up-regulation of their transcription. In our study, we examined whether polyphenols could affect the Nrf2-ARE signalling pathway. Preliminary screening was first carried out using AREc32 cells to find flavonoids which have ARE-inducing ability. Flavonoids, which…
author: Xiao, Han
language: eng
date published: 2010
date modified: 2026-07-24T02:07:31Z
provider: University of Dundee
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Dundee