Engagement of phytoestrogens in breast cancer suppression: Structural classification and mechanistic approach

Tanwar, Ankur Kumar; Dhiman, Neha; Kumar, Amit; Jaitak, Vikas

doi:10.1016/j.ejmech.2020.113037

Cited by 43 publications

(24 citation statements)

References 227 publications

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“…Further, the anti-proliferative potential of the extract was high against the MCF-7 cells, which is considered as an estrogen receptor-positive cell line ( Altharawi et al, 2020 ); on contrary, the cytotoxicity towards MDAMB231 cells, a triple-negative breast cancer cell ( Hero et al, 2019 ), is much lower. At present it is difficult to explain the disparity; however, it is expected that the presence of compounds with estrogenic potential usually known as phytoestrogens such as quercetin may have contributed to this phenomenon ( Tanwar et al, 2021 ). Several of these phytoestrogens are known for their anti-proliferative activities at their dose-dependent nature.…”

Section: Discussionmentioning

confidence: 99%

Phytochemical profiling of Azima tetracantha Lam. leaf methanol extract and elucidation of its potential as a chain-breaking antioxidant, anti-inflammatory and anti-proliferative agent

Malayil

Jose²,

Narayanankutty³

et al. 2021

Saudi Journal of Biological Sciences

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Azima tetracantha, a traditional medicinal plant included in the order Brassicales and family Salvadoraceae, is widely used as a dietary supplement in folklore medicines. The plant is also used for the treatment of rheumatism, diarrhea and other inflammatory disorders. The present investigation focused on the phytochemical composition, radical scavenging, reducing potential and anti-proliferative activities of the A. tetracantha leaves. Quantitative estimation of the polyphenols and flavonoids revealed significantly elevated levels in the methanol extract. Corroborating with this, methanol extract exhibited higher in vitro anti-radical scavenging effect against 2,2-diphenyl-1- picrylhydrazyl (34.14 ± 2.19 μg/mL), and hydrogen peroxide (44.96 ± 1.77 μg/mL), as well as ferric reducing properties (58.24 ± 6.98 μg/mL). The methanolic extract also showed strong lipoxygenase (71.42 ± 6.36 μg/mL) and nitric oxide inhibitory activities (94.23 ± 8.11 μg/mL). Cytotoxic activity against MCF7 cells was found to be higher (IC50= 37.62 ± 2.94 μg/mL), than that of MDAMB231 cells (IC50= 69.11 ± 5.02 μg/mL). The qPCR-based analysis indicated dose-dependent increase in the expression of the pro-apoptotic genes such as executioner caspases and apoptotic protease activating factor-1. Overall, the results indicated the possible use of methanol extract of A. tetracantha leaves as a chain-breaking antioxidant molecule and are capable of inhibiting inflammatory enzymes and the proliferative potential of breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Phytochemical profiling of Azima tetracantha Lam. leaf methanol extract and elucidation of its potential as a chain-breaking antioxidant, anti-inflammatory and anti-proliferative agent

Malayil

Jose²,

Narayanankutty³

et al. 2021

Saudi Journal of Biological Sciences

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“…Other considerations would include the much higher circulating levels of phytoestrogens seen in East Asian men vs European men (79). Phytoestrogens can activate both traditional and cell surface estrogen receptors (80,81). Differences in reproductive hormones and particularly circulating estrogens have been considered as a possible hormonal cause of the dominance of KCNJ5 mutations in APA from women vs men of all races (77,82).…”

Section: Impact Of Race On Genetic Causes Of Aldosterone-producing Adenomamentioning

confidence: 99%

GENETICS IN ENDOCRINOLOGY: Impact of race and sex on genetic causes of aldosterone-producing adenomas

Nanba

Rainey

2021

European Journal of Endocrinology

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Primary aldosteronism (PA) is a common cause of secondary hypertension. Recent technological advances in genetic analysis have provided a better understanding of the molecular pathogenesis of this disease. The application of next-generation sequencing has resulted in the identification of somatic mutations in aldosterone-producing adenoma (APA), a major subtype of PA. Based on the recent findings using a sequencing method that selectively targets the tumor region where aldosterone synthase (CYP11B2) is expressed, the vast majority of APAs appear to harbor a somatic mutation in one of the aldosterone-driver genes, including KCNJ5, ATP1A1, ATP2B3, CACNA1D, CACNA1H, and CLCN2. Mutations in these genes alter intracellular ion homeostasis and enhance aldosterone production. In a small subset of APAs, somatic activating mutations in the CTNNB1 gene, which encodes β-catenin, have also been detected. Accumulating evidence suggests that race and sex impact the somatic mutation spectrum of APA. Specifically, somatic mutations in the KCNJ5 gene, encoding an inwardly rectifying K+ channel, are common in APAs from Asian populations as well as women regardless of race. Associations between APA histology, genotype, and patient clinical characteristics have also been proposed, suggesting a potential need to consider race and sex for the management of PA patients. Herein, we review recent findings regarding somatic mutations in APA and discuss potential roles of race and sex on the pathophysiology of APA as well as possible clinical implications.

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“…Xenoestrogens occur naturally in plants or are chemically synthesized to manufacture consumer goods. These exogenous estrogens directly bind to the ligand-binding domain or other allosteric regions within ER primarily by their structural resemblance to the endogenous estrogens [ 141 , 142 ]. Xenoestrogens exhibit varying affinities to different estrogen receptors identified in humans.…”

Section: Xenoestrogens In Inflammation and Breast Cancermentioning

confidence: 99%

“…Phytoestrogens, also referred to as plant-derived xenoestrogens or dietary estrogens, are polyphenolic or nonsteroidal compounds, naturally synthesized as secondary metabolites in plants [ 141 , 144 ]. Phytoestrogens possess a weak estrogenic activity and interfere with physiological estrogen signaling [ 145 ].…”

Section: Xenoestrogens In Inflammation and Breast Cancermentioning

confidence: 99%

“…In the human gut, phytoestrogens are metabolized into active polyphenolic compounds capable of binding ERs with different affinities [ 146 , 147 ]. Depending on the circulating concentration of the endogenous estrogens and ER, phytoestrogens can evoke estrogenic or antiestrogenic properties that help maintain homeostatic estrogen signaling during estrogen deficiency or when there is overexpression of ER [ 141 , 148 ].…”

Section: Xenoestrogens In Inflammation and Breast Cancermentioning

confidence: 99%

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Natural and Synthetic Estrogens in Chronic Inflammation and Breast Cancer

Maharjan

Wang

et al. 2021

Cancers

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The oncogenic role of estrogen receptor (ER) signaling in breast cancer has long been established. Interaction of estrogen with estrogen receptor (ER) in the nucleus activates genomic pathways of estrogen signaling. In contrast, estrogen interaction with the cell membrane-bound G-protein-coupled estrogen receptor (GPER) activates the rapid receptor-mediated signaling transduction cascades. Aberrant estrogen signaling enhances mammary epithelial cell proliferation, survival, and angiogenesis, hence is an important step towards breast cancer initiation and progression. Meanwhile, a growing number of studies also provide evidence for estrogen’s pro- or anti-inflammatory roles. As other articles in this issue cover classic ER and GPER signaling mediated by estrogen, this review will discuss the crucial mechanisms by which estrogen signaling influences chronic inflammation and how that is involved in breast cancer. Xenoestrogens acquired from plant diet or exposure to industrial products constantly interact with and alter innate estrogen signaling at various levels. As such, they can modulate chronic inflammation and breast cancer development. Natural xenoestrogens generally have anti-inflammatory properties, which is consistent with their chemoprotective role in breast cancer. In contrast, synthetic xenoestrogens are proinflammatory and carcinogenic compounds that can increase the risk of breast cancer. This article also highlights important xenoestrogens with a particular focus on their role in inflammation and breast cancer. Improved understanding of the complex relationship between estrogens, inflammation, and breast cancer will guide clinical research on agents that could advance breast cancer prevention and therapy.

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Engagement of phytoestrogens in breast cancer suppression: Structural classification and mechanistic approach

Cited by 43 publications

References 227 publications

Phytochemical profiling of Azima tetracantha Lam. leaf methanol extract and elucidation of its potential as a chain-breaking antioxidant, anti-inflammatory and anti-proliferative agent

Phytochemical profiling of Azima tetracantha Lam. leaf methanol extract and elucidation of its potential as a chain-breaking antioxidant, anti-inflammatory and anti-proliferative agent

GENETICS IN ENDOCRINOLOGY: Impact of race and sex on genetic causes of aldosterone-producing adenomas

Natural and Synthetic Estrogens in Chronic Inflammation and Breast Cancer

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