Plant natural modulators in breast cancer prevention: status quo and future perspectives reinforced by predictive, preventive, and personalized medical approach

Abstract

In contrast to the genetic component in mammary carcinogenesis, epigenetic alterations are particularly important for the development of sporadic breast cancer (BC) comprising over 90% of all BC cases worldwide. Most of the DNA methylation processes are physiological and essential for human cellular and tissue homeostasis, playing an important role in a number of key mechanisms. However, if dysregulated, DNA methylation contributes to pathological processes such as cancer development and progression. A global hypomethylation of oncogenes and hypermethylation of tumor-suppressor genes are characteristic of most cancer types. Moreover, histone chemical modifications and non-coding RNA-associated multi-gene controls are considered as the key epigenetic mechanisms governing the cellular homeostasis and differentiation states. A number of studies demonstrate dietary plant products as actively affecting the development and progression of cancer. "Nutri-epigenetics" focuses on the influence of dietary agents on epigenetic mechanisms. This approach has gained considerable attention; since in contrast to genetic alterations, epigenetic modifications are reversible affect early carcinogenesis. Currently, there is an evident lack of papers dedicated to the phytochemicals/plant extracts as complex epigenetic modulators, specifically in BC. Our paper highlights the role of plant natural compounds in targeting epigenetic alterations associated with BC development, progression, as well as its potential chemoprevention in the context of preventive medicine. Comprehensive measures are stated with a great potential to advance the overall BC management in favor of predictive, preventive, and personalized medical services and can be considered as "proof-of principle" model, for their potential application to other multifactorial diseases.

Keywords: Breast cancer; Breast cancer prevention; DNA methylations; Epigenetic modulations; Histones chemical modifications; Individual outcomes; Individualized patient profile; Innovation; Natural modulators; Patient stratification; Phytochemicals; Predictive preventive personalized medicine; RNA mechanisms.

Fig. 1

The relevance of epigenetics in the carcinogenesis. Epigenetic mechanisms of carcinogenesis consist of three distinct processes: DNA methylations, histone protein methylations, and acetylations and RNA mechanisms including aberrant activity of siRNA, miRNA, and lncRNA. Ac, acetylation; DNMTs, methyltransferases; Me, methylation

Fig. 2

Mechanism of enhanced tumor-suppressor gene expression through increased promoter demethylation using isolated plant-derived compounds or plant foods. DNMTs, DNA methyltransferases; TET, ten-eleven translocation protein; 5mC, 5-methylcytosine; 5hmC, 5-hydroxymethylcytosine

Fig. 3

The role of plant compounds in the chemical modification of histones. Phytochemicals affect the functions of KMTs, KDMs, HDACs, HATs, and DNMTs and thus regulate genes’ transcription activity. SWI/SNF (SWItch/Sucrose Non-Fermentable), is ATP-dependent nucleosome remodeling protein complex. It is able to restructure the nucleosome to make its DNA accessible during transcription, replication, and DNA repair. DNMTs, DNA methyltransferases; HATs, histone acetyltransferases; HDACs, histone deacetylases; KDMs, lysine demethylases; KMTs, lysine methyltransferases

Fig. 4

Mechanism of action of phytochemicals involving non-coding RNA regulations within breast carcinogenesis. See text for indicated changes as each displayed axis represents the findings of presented studies. Arrows demonstrate specific effect of phytochemicals in female breast cancer model; ↑induction/upregulation, ↓inhibition/reduction. DNMT3b, DNA(cytosine-5-)-methyltransferase 3 beta; Mcl-1, induced myeloid leukemia cell differentiation protein; PTEN, phosphatase and tensin homolog; TIGAR, TP53-inducible glycolysis and apoptosis regulator; T-S, tumor-suppressive