A perspective on dietary phytochemicals and cancer chemoprevention: Oxidative stress, Nrf2, and epigenomics

Zheng Yuan Su, Limin Shu, Tin Oo Khor, Jong Hun Lee, Francisco Fuentes, Ah Ng Tony Kong

Research output: Chapter in Book/Report/Conference proceedingChapter

107 Scopus citations

Abstract

Oxidative stress is caused by an imbalance of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and the antioxidative stress defense systems in cells. ROS/RNS or carcinogen metabolites can attack intracellular proteins, lipids, and nucleic acids, which can result in genetic mutations, carcinogenesis, and other diseases. Nrf2 plays a critical role in the regulation of many antioxidative stress/antioxidant and detoxification enzyme genes, such as glutathione S-transferases (GSTs), NAD(P)H:quinone oxidoreductase 1 (NQO1), UDP-glucuronyl transferases (UGTs), and heme oxygenase-1 (HO-1), directly via the antioxidant response element (ARE). Recently, many studies have shown that dietary phytochemicals possess cancer chemopreventive potential through the induction of Nrf2-mediated antioxidant/detoxification enzymes and anti-inflammatory signaling pathways to protect organisms against cellular damage caused by oxidative stress. In addition, carcinogenesis can be caused by epigenetic alterations such as DNA methylation and histone modifications in tumor-suppressor genes and oncogenes. Interestingly, recent studies have shown that several naturally occurring dietary phytochemicals can epigenetically modify the chromatin, including reactivating Nrf2 via demethylation of CpG islands and the inhibition of histone deacetylases (HDACs) and/or histone acetyltransferases (HATs). The advancement and development of dietary phytochemicals in cancer chemoprevention research requires the integration of the known, and as-yet-unknown, compounds with the Nrf2-mediated antioxidant, detoxification, and anti-inflammatory systems and their in vitro and in vivo epigenetic mechanisms; human clinical efficacy studies must also be performed.

Original languageEnglish (US)
Title of host publicationNatural Products in Cancer Prevention and Therapy
EditorsJohn Pezzuto, Nanjoo Suh
Pages133-162
Number of pages30
DOIs
StatePublished - 2013

Publication series

NameTopics in Current Chemistry
Volume329
ISSN (Print)0340-1022

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

Keywords

  • Antioxidant response
  • Inflammation
  • Keap1
  • Nrf2

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