Dietary Phytochemicals and Cancer Chemoprevention: A Perspective on Oxidative Stress, Inflammation, and Epigenetics

Abstract

Oxidative stress occurs when cellular reactive oxygen species levels exceed the self-antioxidant capacity of the body. Oxidative stress induces many pathological changes, including inflammation and cancer. Chronic inflammation is believed to be strongly associated with the major stages of carcinogenesis. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a crucial role in regulating oxidative stress and inflammation by manipulating key antioxidant and detoxification enzyme genes via the antioxidant response element. Many dietary phytochemicals with cancer chemopreventive properties, such as polyphenols, isothiocyanates, and triterpenoids, exert antioxidant and anti-inflammatory functions by activating the Nrf2 pathway. Furthermore, epigenetic changes, including DNA methylation, histone post-translational modifications, and miRNA-mediated post-transcriptional alterations, also lead to various carcinogenesis processes by suppressing cancer repressor gene transcription. Using epigenetic research tools, including next-generation sequencing technologies, many dietary phytochemicals are shown to modify and reverse aberrant epigenetic/epigenome changes, potentially leading to cancer prevention/treatment. Thus, the beneficial effects of dietary phytochemicals on cancer development warrant further investigation to provide additional impetus for clinical translational studies.

Peer Review #1 of "Phytochemical composition and in vitro antioxidant activities of Citrus sinensis peel extracts (v0.2)"

“…Catechin is found abundantly in tea extracts and is well known for its multiple health benefits including anti-aging, anti-diabetic and anti-cancer effects (Pandey & Rizvi, 2009). Epigallocatechin and apigenin which were also present in high abundance in the extracts were suggested to be able to reverse epigenetic changes in disease prevention and regulate a number of biological processes (Li et al, 2016;Shankar et al, 2016;Zhou, Yang and Kong, 2017). On the other hand, rutin was claimed to demonstrate beneficial biological properties including antioxidant, anti-inflammatory and anticarcinogenic properties (Rawson, Ho and Li, 2014).…”

Ação Quimiopreventiva dos Fitoquímicos por meio da Regulação do Fator de Transcrição Nrf2: Revisão Integrativa da Literatura

“…O estresse oxidativo induz muitas alterações patológicas, incluindo inflamação e câncer. Acredita-se que a inflamação crônica esteja fortemente associada aos principais estágios da carcinogênese 23 .…”

“…De acordo com Li et al 23 , existem muitos fitoquímicos com propriedades quimiopreventivas do câncer, exercendo funções antioxidantes e anti-inflamatórias, por meio da ativação da via Nrf2. O fator de transcrição Nrf2 pertence à família cap'n'collar de fatores básicos de transcrição de região-leucina, e desempenha um papel crucial na regulação do estresse oxidativo e da inflamação, manipulando os principais genes da enzima antioxidante e da desintoxicação, por intermédio do elemento de resposta antioxidante (ERA) 30 .…”

EGCG Containing Combined Dietary Supplement Affects Telomeres and Epigenetic Regulation

“…Phytochemicals such as EGCG are capable of affecting aberrant epigenetic events by various mechanisms including inhibition of DNA methyltransferase (DNMT)-the enzyme responsible for adding methylgroups to DNA, modulation of histone acetylation via histone deacetylase (HDAC), histone acetyltransferase (HAT) inhibition or influence on noncoding RNA expression [40][41][42][43][44]. Thus, dietary phytochemicals exhibiting epigenetic properties such as EGCG could prevent disease development and premature aging [44,45] Furthermore, especially nutrients involved in the metabolism of methyl groups such as methionine, choline, vitamin B12 and folic acid are suggested to play a central role in maintaining DNA methylation patterns while aging [46].…”

“…Thus, dietary phytochemicals exhibiting epigenetic properties such as EGCG could prevent disease development and premature aging [44,45] Furthermore, especially nutrients involved in the metabolism of methyl groups such as methionine, choline, vitamin B12 and folic acid are suggested to play a central role in maintaining DNA methylation patterns while aging [46].…”