Aglycone rich extracts of phytoestrogens cause ROS-mediated DNA damage in breast carcinoma cells

Dutta, Shreelekha; Khanna, Aparna

doi:10.1016/j.biopha.2016.11.032

Cited by 10 publications

(7 citation statements)

References 30 publications

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“…It would then act to trigger apoptosis through the mitochondria pathway. A previous study also reported similar results in which the aglycone-rich extract of phytoestrogens could induce an increase of ROS, which could then modulate the mitochondrial membrane potential and trigger and release certain mitochondrial proapoptotic factors such as cytochrome c, all of which would ultimately activate the mitochondria-mediated apoptosis pathway [13,44].…”

Section: Discussionsupporting

confidence: 53%

Pentagalloyl Glucose‐ and Ethyl Gallate‐Rich Extract from Maprang Seeds Induce Apoptosis in MCF‐7 Breast Cancer Cells through Mitochondria‐Mediated Pathway

Kantapan

Paksee²,

Chawapun

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Bouea macrophylla Griffith, locally known as maprang, has important economic value as a Thai fruit tree. The maprang seed extract (MPSE) has been shown to exhibit antibacterial and anticancer activities. However, the bioactive constituents in MPSE and the molecular mechanisms underlying these anticancer activities remain poorly understood. This study aims to identify the active compounds in MPSE and to investigate the mechanisms involved in MPSE-induced apoptosis in MCF-7 treated cancer cells. The cytotoxic effect was determined by MTT assay. The apoptosis induction of MPSE was evaluated in terms of ROS production, mitochondrial membrane potential depolarization, and apoptosis-related gene expression. The compounds identified by HPLC and LC/MS analysis were pentagalloyl glucose, ethyl gallate, and gallic acid. MPSE treatment decreased cell proliferation in MCF-7 cells, and MPSE was postulated to induce G2/M phase cell cycle arrest. MPSE was found to promote intracellular ROS production in MCF-7 treated cells and to also influence the depolarization of mitochondrial membrane potential. In addition, MPSE treatment can lead to increase in the Bax/Bcl-2 gene expression ratio, suggesting that MPSE-induced apoptosis is mitochondria-dependent pathway. Our results suggest that natural products obtained from maprang seeds have the potential to target the apoptosis pathway in breast cancer treatments.

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Section: Discussionsupporting

confidence: 53%

Pentagalloyl Glucose‐ and Ethyl Gallate‐Rich Extract from Maprang Seeds Induce Apoptosis in MCF‐7 Breast Cancer Cells through Mitochondria‐Mediated Pathway

Kantapan

Paksee²,

Chawapun

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…Because the reduction of mitochondrial potential and mitochondrial dysfunction are accompanied by damage to the respiratory chain and overproduction of ROS, we suppose that extracts constituents antioxidative properties prevented spreading of radicals. That mode of action was demonstrated for soya beans and flax; see aglycon rich extracts [32]. They were able to decrease mitochondrial membrane potential, and the activities of main radical scavenging enzymes, SOD (superoxide dismutase) and GPx (glutathione peroxidase), leading to the induction of apoptosis in MCF-7 and MDA-MB-231 cells.…”

Section: Trifolium Pratense L As a Chemopreventive Agentmentioning

confidence: 84%

“…Biochanin A is known as strong scavenger of ROS, activator of SOD (superoxide dismutase) enzyme activity and reducer of COX-2 expression [31]. However, there is growing evidence of polyphenols' reactions with nonpolar compounds present in the hydrophobic inner membrane layer [18,32,33]. Thus, the second way of protection of the cellular Control cells were not exposed to any compound but the vehicle; values are means ± standard deviations from at least three independent experiments; statistical significance was calculated versus control cells (untreated); *** p ≤ 0.001.…”

Section: Trifolium Pratense L As a Chemopreventive Agentmentioning

confidence: 99%

The Effects of Trifolium pratense L. Sprouts’ Phenolic Compounds on Cell Growth and Migration of MDA-MB-231, MCF-7 and HUVEC Cells

Zakłos‐Szyda

Budryn

2020

Nutrients

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Uncontrolled growth and migration and invasion abilities are common for cancer cells in malignant tumors with low therapeutic effectiveness and high mortality and morbidity. Estrogen receptor β (ERβ), as a member of the nuclear receptor superfamily, shows potent tumor suppressive activities in many cancers. Phytoestrogens’ structural resemblance to 17 β-estradiol allows their binding to ERβ isoform predominantly, and therefore, expression of genes connected with elevated proliferation, motility and invasiveness of cancer cells may be downregulated. Among polyphenolic compounds with phytoestrogenic activity, there are isoflavones from Trifolium pratense L. (red clover) sprouts, containing high amounts of formononetin and biochanin A and their glycosides. To determine the source of the most biologically active isoflavones, we obtained four extracts from sprouts before and after their lactic fermentation and/or β-glucosidase treatment. Our previous results of ITC (isothermal titration calorimetry) modelling and a docking simulation showed clover isoflavones’ affinity to ERβ binding, which may downregulate cancer cell proliferation and migration. Thus, the biological activity of T. pratense sprouts’ extracts was checked under in vitro conditions against highly invasive human breast cancer cell line MDA-MB-231 and non-invasive human breast cancer cell line MCF-7 cells. To compare extracts’ activities acquired for cancer cells with those activities against normal cells, as a third model we choose human umbilical vein endothelial cells (HUVEC), which, due to their migration abilities, are involved in blood vessel formation. Extracts obtained from fermented sprouts at IC0 dosages were able to inhibit migration of breast cancer cells through their influence on intracellular ROS generation; membrane stiffening; adhesion; regulation of MMP-9, N-cadherin and E-cadherin at transcriptional level; or VEGF secretion. Simultaneously, isolated phenolics revealed no toxicity against normal HUVEC cells. In the manuscript, we proposed a preliminary mechanism accounting for the in vitro activity of Trifolium pratense L. isoflavones. In this manner, T. pratense sprouts, especially after their lactic fermentation, can be considered a potent source of biological active phytoestrogens and a dietary supplement with anti-cancer and anti-invasion properties.

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“…MDA can damage tissues and cells. 28,29 At the same time, the level of MDA reects the extent of ROS. SOD can specically bind to superoxide anions in vivo and can act synergistically with GSH-Px to prevent lipid peroxidation and its metabolites from damaging the body.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of a T-2 toxin-producingFusarium poaestrain and the anti-tumor effect of the T-2 toxin on human hepatoma cell line SMMC-7721

et al. 2019

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Aglycone rich extracts of phytoestrogens cause ROS-mediated DNA damage in breast carcinoma cells

Cited by 10 publications

References 30 publications

Pentagalloyl Glucose‐ and Ethyl Gallate‐Rich Extract from Maprang Seeds Induce Apoptosis in MCF‐7 Breast Cancer Cells through Mitochondria‐Mediated Pathway

Pentagalloyl Glucose‐ and Ethyl Gallate‐Rich Extract from Maprang Seeds Induce Apoptosis in MCF‐7 Breast Cancer Cells through Mitochondria‐Mediated Pathway

The Effects of Trifolium pratense L. Sprouts’ Phenolic Compounds on Cell Growth and Migration of MDA-MB-231, MCF-7 and HUVEC Cells

Identification and characterization of a T-2 toxin-producingFusarium poaestrain and the anti-tumor effect of the T-2 toxin on human hepatoma cell line SMMC-7721

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