Exploring the Biological Activity and Mechanism of Xenoestrogens and Phytoestrogens in Cancers: Emerging Methods and Concepts

Abstract

Xenoestrogens and phytoestrogens are referred to as “foreign estrogens” that are produced outside of the human body and have been shown to exert estrogen-like activity. Xenoestrogens are synthetic industrial chemicals, whereas phytoestrogens are chemicals present in the plant. Considering that these environmental estrogen mimics potentially promote hormone-related cancers, an understanding of how they interact with estrogenic pathways in human cells is crucial to resolve their possible impacts in cancer. Here, we conducted an extensive literature evaluation on the origins of these chemicals, emerging research techniques, updated molecular mechanisms, and ongoing clinical studies of estrogen mimics in human cancers. In this review, we describe new applications of patient-derived xenograft (PDX) models and single-cell RNA sequencing (scRNA-seq) techniques in shaping the current knowledge. At the molecular and cellular levels, we provide comprehensive and up-to-date insights into the mechanism of xenoestrogens and phytoestrogens in modulating the hallmarks of cancer. At the systemic level, we bring the emerging concept of window of susceptibility (WOS) into focus. WOS is the critical timing during the female lifespan that includes the prenatal, pubertal, pregnancy, and menopausal transition periods, during which the mammary glands are more sensitive to environmental exposures. Lastly, we reviewed 18 clinical trials on the application of phytoestrogens in the prevention or treatment of different cancers, conducted from 2002 to the present, and provide evidence-based perspectives on the clinical applications of phytoestrogens in cancers. Further research with carefully thought-through concepts and advanced methods on environmental estrogens will help to improve understanding for the identification of environmental influences, as well as provide novel mechanisms to guide the development of prevention and therapeutic approaches for human cancers.

Bisphenol-A/Radiation mediated inflammatory response activates EGFR/KRAS/ERK1/2 signaling pathway leads to lung carcinogenesis incidence

“…GPER is involved in a number of carcinogenesis processes, including angiogenesis, cellular migration, and adhesion. 21 As shown in Figure 1, the levels of GRP and gene transcript of GPER were elevated significantly in IR and BPA relative to the control group ( p < 0.05). An additional increase in the IR+BPA relative to the relevant IR and BPA group values was observed.

Figure 1.The GRP/GPER signaling factors reinforce the MMP-2 and MMP-9 in lung rats exposed to BPA/IR.

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Xeno-Estrogenic Pesticides and the Risk of Related Human Cancers

“…Risk of breast, endometrium, and ovary cancers in females and risk of prostate and testis cancers in males are estrogen-dependent to some extent [ 71 ]. Studies indicate a strong relation between exposure to estrogens as the principal risk factor in the development of these estrogen-mediated cancers [ 15 , 16 , 18 , 19 , 32 , 38 , 57 , 60 , 62 , 70 ].…”

“…Other natural and man-made compounds are known to exist with xeno-estrogenic potential in the environment, such as butylated hydroxyanisole, phthalate esters, nonylphenol, benzyl butyl phthalate, and bisphenol-A, etc. [ 19 ]. However, pesticides are the most potent xeno-estrogens amongst all the chemicals because the estrogenic potency and half-life in the environment of these compounds exceed those of any other compound [ 3 , 4 , 5 ].…”

Los Disruptores Endocrinos Como Obesógenos Ambientales: Efectos en Proteínas Adipogénicas Clave

“…Se ha encontrado que los parabenos inducen efectos obesogénicos en modelos experimentales (Hu et al, 2017;Artacho-Cordón et al, 2018). Por otro lado, algunos EDC como los fitoestrógenos y micoestrógenos provienen de fuentes naturales como plantas y hongos, y podrían contribuir al desarrollo de enfermedades como cáncer (Wang et al, 2021).…”