Impact of soy isoflavones on the epigenome in cancer prevention.

Maria Pudenz,Clarissa Gerhauser,Kevin Roth

doi:10.3390/nu6104218

Maria Pudenz, Clarissa Gerhauser + Show 1 more

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https://doi.org/10.3390/nu6104218

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Abstract

Isoflavones (IF) such as genistein are cancer preventive phytochemicals found in soy and other legumes. Epidemiological studies point to a reduced risk for hormone‑dependent cancers in populations following a typical Asian diet rich in soy products. IF act as phytoestrogens and prevent tumorigenesis in rodent models by a broad spectrum of bioactivities. During the past 10 years, IF were shown to target all major epigenetic mechanisms regulating gene expression, including DNA methylation, histone modifications controlling chromatin accessibility, and non-coding RNAs. These effects have been suggested to contribute to cancer preventive potential in in vitro and in vivo studies, affecting several key processes such as DNA repair, cell signaling cascades including Wnt-signaling, induction of apoptosis, cell cycle progression, cell proliferation, migration and invasion, epithelial-mesenchymal transition (EMT), metastasis formation and development of drug-resistance. We here summarize the state-of-the-art of IF affecting the epigenome in major hormone-dependent, urogenital, and gastrointestinal tumor types and in in vivo studies on anti-cancer treatment or developmental aspects, and short-term intervention studies in adults. These data, while often requiring replication, suggest that epigenetic gene regulation represents an important novel target of IF and should be taken into consideration when evaluating the cancer preventive potential of IF in humans.

Highlights

DNA methylation analysis was performed in peripheral blood mononuclear cells (PBMCs) collected before and after intervention for the repetitive sequence LINE1 and a series of tumor suppressor genes (RASSF1A and the cell cycle regulators p16 (CDKN2A) and ARF), and genes involved in DNA repair (MLH1) and folate metabolism (MTHFR, methylene-tetrahydrofolate reductase)
Earlier studies focused on DNA methylation changes and mainly tested whether IF might be able to reverse cancer-associated aberrations in DNA methylation, especially silencing of tumor suppressor genes (TSGs) such as RARβ2, BTG3, PTEN and ATM, genes involved in DNA repair (MGMT, BRCA1, BRCA2, GSTP1), cell signaling, and cell cycle regulators (p16)
Since reduced levels of enzymatic activity can result from direct enzyme inhibitory effects, and from changes in gene or protein expression, expression levels should be analyzed in parallel

Summary

Introduction

One of the recent dietary recommendations of the World Cancer Research Fund (WCRF) is to increase consumption of plant foods, whole grains, nuts and legumes [2]. Lentils and chickpeas are a good dietary source of isoflavones (IF), a class of plant estrogens (phytoestrogens) predominantly found as glycoside conjugates. Dietary intake of IF varies drastically between Western and Asian Countries. As fermented soy products like Tofu, Tempeh, Miso and soy sauce are part of the regular diet in many Asian countries, dietary intake of IF has been estimated from 15 mg/day in China [4] and 60 mg/day in Singapore [5] up to 200 mg/day in Japan [6]. In addition to differences in uptake, variability in the gut microbiota composition that may influence IF bioavailability, as well as gene polymorphisms may explain discrepancies and individual variability observed in clinical studies investigating biological effects of IF [10]

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