Role of Dietary Antioxidants in p53-Mediated Cancer Chemoprevention and Tumor Suppression

J. P.Jose Merlin, H. P.Vasantha Rupasinghe, Graham Dellaire, Kieran Murphy

Research output: Contribution to journalReview articlepeer-review

52 Citations (Scopus)

Abstract

Cancer arises through a complex interplay between genetic, behavioral, metabolic, and environmental factors that combined trigger cellular changes that over time promote malignancy. In terms of cancer prevention, behavioral interventions such as diet can promote genetic programs that may facilitate tumor suppression; and one of the key tumor suppressors responsible for initiating such programs is p53. The p53 protein is activated by various cellular events such as DNA damage, hypoxia, heat shock, and overexpression of oncogenes. Due to its role in cell fate decisions after DNA damage, regulatory pathways controlled by p53 help to maintain genome stability and thus "guard the genome"against mutations that cause cancer. Dietary intake of flavonoids, a C15 group of polyphenols, is known to inhibit cancer progression and assist DNA repair through p53-mediated mechanisms in human cells via their antioxidant activities. For example, quercetin arrests human cervical cancer cell growth by blocking the G2/M phase cell cycle and inducing mitochondrial apoptosis through a p53-dependent mechanism. Other polyphenols such as resveratrol upregulate p53 expression in several cancer cell lines by promoting p53 stability, which in colon cancer cells results in the activation of p53-mediated apoptosis. Finally, among vitamins, folic acid seems to play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in patients with premalignant lesions by significantly increased expression of p53. In this review, we discuss the role of these and other dietary antioxidants in p53-mediated cell signaling in relation to cancer chemoprevention and tumor suppression in normal and cancer cells.

Original languageEnglish
Article number9924328
JournalOxidative Medicine and Cellular Longevity
Volume2021
DOIs
Publication statusPublished - 2021

Bibliographical note

Publisher Copyright:
© 2021 J. P. Jose Merlin et al.

ASJC Scopus Subject Areas

  • Biochemistry
  • Ageing
  • Cell Biology

PubMed: MeSH publication types

  • Journal Article
  • Review

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