The modulatory role of low concentrations of bisphenol A on tamoxifen-induced proliferation and apoptosis in breast cancer cells

Huang, Bin; Luo, Nao; Wu, Xiaoni; Xu, Zhixiang; Wang, Xiaoxia; Pan, Xuejun

doi:10.1007/s11356-018-3780-6

Cited by 20 publications

(18 citation statements)

References 55 publications

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“…These results suggested that anticancer effect of guajadial enriched fraction does not involve exclusively the action on estrogenic receptors, but also cell death mechanism activation initiated by exposure of phosphatidylserine residues and interruption G1-phase cell cycle. The tamoxifen mechanism of action is well-established on cancer cells and consists in inhibiting DNA synthesis, inducing apoptosis and blocking cell cycle in G1 phase [37]. Similarly, F FINAL fraction exhibited an activity on G1 phase of MCF-7 BUS cell cycle.…”

Section: Discussionmentioning

confidence: 97%

Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves (Psidium guajava L.)

et al. 2020

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The research of natural products has allowed for the discovery of biologically relevant compounds inspired by plant secondary metabolites, which contributes to the development of many chemotherapeutic drugs used in cancer treatment. Psidium guajava leaves present a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids, and triterpenes as the major bioactive constituents. Guajadial, a caryophyllene-based meroterpenoid, has been studied for potential anticancer effects tested in tumor cells and animal experimental models. Moreover, guajadial has been reported to have a mechanism of action similar to tamoxifen, suggesting this compound as a promisor phytoestrogen-based therapeutic agent. Herein, the anti-estrogenic action and anti-proliferative activity of guajadial is reported. The enriched guajadial fraction was obtained by sequential chromatographic techniques from the crude P. guajava dichloromethane extract showing promising anti-proliferative activity in vitro with selectivity for human breast cancer cell lines MCF-7 and MCF-7 BUS (Total Growth Inhibition = 5.59 and 2.27 µg·mL−1, respectively). Furthermore, evaluation of anti-estrogenic activity in vivo was performed demonstrating that guajadial enriched fraction inhibited the proliferative effect of estradiol on the uterus of pre-pubescent rats. These results suggest a relationship between anti-proliferative and anti-estrogenic activity of guajadial, which possibly acts in tumor inhibition through estrogen receptors due to the compounds structural similarity to tamoxifen.

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Section: Discussionmentioning

confidence: 97%

Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves (Psidium guajava L.)

et al. 2020

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“…Resistance to tamoxifen of ER-positive tumors can be caused by a loss of ER [158], its mutation, or posttranslational modification [159] among others. It was shown that BPA is involved in chemoresistance [160] and notably in resistance to tamoxifen in ER-positive tumor cell lines [161] by decreasing tamoxifen-induced apoptosis and increasing gene expression of ERRα, which contributes to resistance to tamoxifen [162] and cell proliferation [157]. Another study demonstrated that an ERα variant could be induced by BMP2 [128] and may be involved in resistance to tamoxifen [163].…”

Section: Discussionmentioning

confidence: 99%

A Potential New Mechanism for Bisphenol Molecules to Initiate Breast Cancer through Alteration of Bone Morphogenetic Protein Signaling in Stem Cells and Their Microenvironment

Guyot¹,

Maguer-Satta²

2020

Breast Cancer Biology

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Endocrine disruptors interfere with endocrine-mediated regulations of cell or organ functions. Estrogens are one of the main hormones altered by endocrine disruptors like bisphenol A (BPA). Stem cells are active from embryogenesis to late stages of adult life. Their unique properties, such as an extended lifespan and low cycling features, render these cell privileged targets of long-term exposure to numerous factors. Therefore, stem cells are likely to be affected following exposure to endocrine disruptors. One of the major signaling pathways involved in stem cell regulation is the bone morphogenetic protein (BMP) pathway. The BMP pathway is known for its involvement in numerous physiological and pathophysiological processes. Exposure of human mammary stem cells to pollutants such as BPA initiates fundamental changes in stem cells, in particular by altering major elements of BMP signaling, such as receptor expression and localization. Lastly, BPA and its substitute bisphenol S (BPS) have similar impacts on BMP signaling despite their different ER-binding properties, supporting the hypothesis that their biological effects cannot be extrapolated only from their interaction with ERα66. We review recent discoveries in this field and discuss their implications for cancer diagnosis, prevention, and treatment, as well as their relevance for studies on endocrine disruptors.

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“…were promoted following combined treatment with low-concentration quercetin, which may be associated with tamoxifen-induced treatment resistance. 19,36 However, tamoxifen combined with highconcentration quercetin further downregulated them, which are positively correlated with the ERs' expression levels ( Figure 6F). Figure 6E).…”

Section: Low-concentration Quercetin Suppressed Tamoxifen-induced Cmentioning

confidence: 92%

“…The real-time quantitative polymerase chain reaction (RT-qPCR) was applied to analyze the expression levels of several desired genes involved in cell proliferation-and apoptosis-related signaling pathways, according to our previous studies. 19,23 The validated primers were shown in Table S1. The mRNA transcription levels of target genes were calculated with the 2 −ΔΔCt method, and β-actin served as the endogenous control for internal normalization.…”

Section: Rna Extraction and Rt-qpcr Assaymentioning

confidence: 99%

“…18 Unfortunately, patients with ER-negative breast cancer were unresponsive to antiestrogens like tamoxifen. 19,20 Moreover, there still large amounts of patients who failed to respond to tamoxifen therapy or even developed tamoxifen resistance. 21 To overcome these limitations, numerous studies have been turned to explore novel anticancer agents existed in medicinal plants and nutriment for breast cancer prolonged therapy.…”

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confidence: 99%

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Quercetin exerts bidirectional regulation effects on the efficacy of tamoxifen in estrogen receptor‐positive breast cancer therapy: An in vitro study

Zhao

Zheng

et al. 2020

Environmental Toxicology

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Tamoxifen was widely applied in the therapy of estrogen receptor (ER)-positive breast cancer. With the purpose of determining the potential impacts of quercetin on its effectiveness, MCF-7 cells were selected as the in vitro model and several cellular biological behaviors (ie, cell proliferation, migration, invasion, cycle, apoptosis, and oxidative stress) were investigated. As results, quercetin showed contrasting doseresponse to cellular behaviors dependent on the ROS-regulated p53 signaling pathways. In detail, quercetin promoted cell proliferation and inhibited cell apoptosis at low concentrations, whereas high-concentration resulted in apoptosis induction. Moreover, quercetin at a low concentration significantly inhibited tamoxifen-induced antiproliferation in MCF-7 cells, whereas high concentrations enhanced cell apoptosis in a synergetic manner. The real-time quantitative polymerase chain reaction analysis further implied that quercetin exerted its dual roles in tamoxifen-induced antiproliferative effects by regulated the gene expression involved in cell metastasis, cycle, and apoptosis through the ER pathways. Our present study provides a considerable support to the combination of quercetin and tamoxifen on human ER-positive breast carcinoma management.

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The modulatory role of low concentrations of bisphenol A on tamoxifen-induced proliferation and apoptosis in breast cancer cells

Cited by 20 publications

References 55 publications

Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves (Psidium guajava L.)

Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves (Psidium guajava L.)

A Potential New Mechanism for Bisphenol Molecules to Initiate Breast Cancer through Alteration of Bone Morphogenetic Protein Signaling in Stem Cells and Their Microenvironment

Quercetin exerts bidirectional regulation effects on the efficacy of tamoxifen in estrogen receptor‐positive breast cancer therapy: An in vitro study

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