Title:Environmental Toxicant Exposure and Cancer: The Role of Epigenetic Changes and Protection by Phytochemicals
Volume: 22
Issue: 2
Author(s): Yunes Panahi, Fatemeh Beiraghdar, Amirali Amirhamzeh, Zohreh Poursaleh, Alireza Saadat and Amirhossein Sahebkar
Affiliation:
Keywords:
Epigenetics, carcinogenesis, cellular reprogramming, polyphenols, STAT-3, miRNA, DNA methylation, histone modification.
Abstract: Exposure to environmental toxicants is a well-documented predisposing factor for
cancer. Although genetic alterations have long been known to occur through exposure to some environmental carcinogens, there is another
layer of genome regulatory system named epigenetic system. Epigenetics is defined as any reversible and heritable change in cellular
patterns of gene expression that does not alter DNA sequence. This layer of gene control plays a key role in early stages of carcinogenesis
by reprogramming cells to what is known as cancer stem cells, a process with great similarities to somatic cell reprogramming
into “induced pluripotent stem cell”. Environmental toxicants could directly promote carcinogenesis through disturbing promoter CpG island
hypermethylation, and silencing of tumor suppressor genes, hypomethylation of transposable elements and genomic instability induced
by environmental toxicants. Environmental toxicants could also indirectly affect epigenetic programming of nucleus through inducing
inflammatory signaling pathways that converge on NF-κB or STAT3 activation. Considering the reversibility of epigenetic alterations
and their pivotal role in early carcinogenesis, reversion of these alterations could be a promising approach for chemoprevention. Selected
phytochemicals have shown desirable effects through regulation of the most important epigenetic mechanisms including DNA
methylation, histone modifications and microRNA expression, as well as modulation of SIRT-1 and STAT-3 signaling pathways. The
present review aims to outline the epigenetic mechanisms underlying carcinogenic effects of environmental toxicants, and the protective
effects of phytochemicals in reversing epigenetic aberrations in the regulatory pathways steering normal cell homeostasis.