Effects of the environmental estrogens bisphenol A, o,p′-DDT, p-tert-octylphenol and coumestrol on apoptosis induction, cell proliferation and the expression of estrogen sensitive molecular parameters in the human breast cancer cell line MCF-7

Diel, Patrick; Olff, Sabine; Schmidt, Simone; Michna, H.

doi:10.1016/s0960-0760(01)00173-x

Cited by 91 publications

(54 citation statements)

References 34 publications

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“…Sex hormones have been shown to modulate both Th1 and Th2 immunity in various mouse models, and implicated in the sex-based difference in incidence of allergic diseases [22,23]. However, it appeared that hormonal activities were not relevant to the effect of these EDC on the Th development, since all three EDC regardless of their estrogenic (BP and OP [24,25]) or androgenic (TBT [15]) activities showed similar promotion of Th2 polarization. Our prediction was partly supported by recent studies showing that OP promotes Th2 development independently of estrogen receptor [26,27].…”

Section: P<001) These Results Suggest That Edc Might Exacerbate Airmentioning

confidence: 99%

Endocrine disruptors that deplete glutathione levels in APC promote Th2 polarization in mice leading to the exacerbation of airway inflammation

et al. 2006

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Endocrine‐disrupting chemicals (EDC) are ubiquitous in environment and may have various undesirable effects on human health. In the present study, we have shown that some EDC [benzophenone, p‐octylphenol, and tributyltin chloride (TBT)] promoted strong Th2 polarization via suppression and augmentation of Th1 and Th2 development, respectively, from naive CD4+ T cells primed with anti‐CD3 and splenic antigen‐presenting cells (APC). The effect was indicated to be indirect via suppression of IL‐12 production and augmentation of IL‐10 production of APC, which are critical for the Th1 and Th2 development, respectively. Such modulation of cytokine production by EDC was associated with reduction of intracellular glutathione levels in APC. IL‐10 deprivation or the addition of N‐acetylcysteine, which replenishes intracellular glutathione level during priming, cancelled the effect of EDC on the promotion of Th2 polarization. Oral administration of TBT, which most effectively promoted Th2 polarization in vitro, exacerbated airway inflammation in a murine model of allergic asthma with concomitant enhancement of Th2‐type immunity. Collectively these results suggest that EDC such as benzophenone, p‐octylphenol, and TBT promote Th2 polarization indirectly via the depletion of glutathione in APC and subsequent modulation of IL‐10 and IL‐12 production that might result in the exacerbation of allergic diseases.

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Section: P<001) These Results Suggest That Edc Might Exacerbate Airmentioning

confidence: 99%

Endocrine disruptors that deplete glutathione levels in APC promote Th2 polarization in mice leading to the exacerbation of airway inflammation

et al. 2006

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“…Based on the results of studies showing that both ERα protein and mRNA levels were decreased markedly in MCF-7 cells after addition of 17β-estradiol [30][31][32], it is suggested that the reduced levels of cytosolic ERs could be the result of translocation of ERs to the nucleus. Furth ermore, Diel et al [30] demonstrated that the reduction of ERα protein l e v e l a f t e r a d m i n i s t r a t i o n o f p r o b a b l e environmental estrogens (DDT and coumestrol) was comparable to the effect of 17β-estradiol, indicating that these compounds act as weak estrogen agonists in MCF-7 cells. Our results similarly revealed that sumithrin induced significant decreases in both ERα and ERβ protein levels.…”

Section: Discussionmentioning

confidence: 99%

Assessing Estrogenic Activity of Pyrethroid Insecticides Using In Vitro Combination Assays

et al. 2004

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Abstract. Pyrethroid insecticides are among the most commonly used classes of insecticides worldwide, but their endocrine disrupting activities remain unclear. Therefore, in the present study, we examined the estrogenic activities of pyrethroid insecticides in E-screen and competition binding assays. In addition, we measured estrogen receptor (ER) protein and pS2 mRNA levels in human breast cancer cells (MCF-7 BUS) to clarify the mechanism of their estrogenicity. Seven pyrethroid insecticides (bioallethrine, cypermethrin, deltamethrin, fenvalerate, permethrin, sumithrin, and tetramethrin) were tested because of their worldwide usage. In addition, 17β-estradiol was tested as a positive control. As expected, 17β-estradiol significantly increased MCF-7 BUS cell proliferation at concentrations of 10 -11 M and above. Of the pyrethroid insecticides tested, only sumithrin increased MCF-7 BUS cell proliferation in a dose-dependent manner; the maximum induction of cell proliferation was observed at a dose of 10 -5 M. In the anti-estrogenic activity test, bioallethrin, fenvalerate, and permethrin significantly inhibited 17β-estradiol-induced MCF-7 BUS cell proliferation at 10 -6 M, a concentration comparable to the effective dose (10 -9 M) of ICI 182,780, a pure ER antagonist. However, none of the pyrethroid insecticides competitively inhibited the binding of [ 3 H]estradiol to rat uterus ERs in competition binding assays. Both 17β-estradiol (10 -10 M) and sumithrin (10 -5 M) decreased the levels of cytosolic ERα and ERβ protein expression significantly as compared with the vehicle control. In addition, 17β-estradiol (10 -10 M) increased pS2 mRNA expression markedly, and sumithrin significantly increased pS2 mRNA levels in a dose-dependent manner. The other six compounds tested in the present study did not affect ER protein levels or pS2 mRNA levels. These results suggest that certain pyrethroid insecticides may be considered to be estrogen-like chemicals that act through pathways other than direct ER binding, and may function as endocrine modulators in both wildlife and humans.

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“…The tubes were placed at 4 8C in darkness for 4 h before flow cytometric analysis. The cell cycle analysis was performed as described by Diel et al (2002).…”

Section: Cell Cycle Analysismentioning

confidence: 99%

C2C12 myoblastoma cell differentiation and proliferation is stimulated by androgens and associated with a modulation of myostatin and Pax7 expression

Diel¹,

Baadners²,

Schlüpmann³

et al. 2008

Journal of Molecular Endocrinology

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Androgens are modulators of skeletal muscle adaptation and regeneration processes. The control of satellite cell activity is a key mechanism during this process. In this study, we analyzed the ability of dihydrotestosterone (DHT) and anabolic steroids to induce and modulate the differentiation of C2C12 myoblastoma cells toward myotubes. C2C12 cells were dose-dependently treated with DHT and anabolic steroids. The time-dependent effects on differentiation were measured and correlated with the expression of genes involved in the regulation of satellite cell activity. The distribution of C2C12 cells within the cell cycle was measured by flow cytometry and differentiation by creatine kinase (CK) activity. Gene expression was analyzed using quantitative real-time PCR and confocal microscopy. The treatment with DHT and anabolic steroids resulted in a stimulation of C2C12 cell proliferation and CK activity. The antiandrogen flutamide was able to antagonize this effect. The expression of the androgen receptor, SOX8, SOX9, Delta, Notch, myostatin, and paired box gene7 (Pax7) was modulated by androgens. The treatment with DHT and anabolic steroids resulted in a strong stimulation of myostatin expression not only in undifferentiated cells but also in myotubes. The stimulation could be antagonized by flutamide. The expression of Pax7 was detectable in C2C12 cells early after treatment with DHT. Our results demonstrate that the key mechanisms of satellite cell differentiation are modulated by androgens. Androgens stimulate the proliferation of C2C12 cells, accelerate the process of differentiation, and increase the expression of myostatin in undifferentiated and differentiated cells. Our findings may have implications not only for the treatment of muscular diseases but also for the improvement of doping analytical methods.

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Effects of the environmental estrogens bisphenol A, o,p′-DDT, p-tert-octylphenol and coumestrol on apoptosis induction, cell proliferation and the expression of estrogen sensitive molecular parameters in the human breast cancer cell line MCF-7

Cited by 91 publications

References 34 publications

Endocrine disruptors that deplete glutathione levels in APC promote Th2 polarization in mice leading to the exacerbation of airway inflammation

Endocrine disruptors that deplete glutathione levels in APC promote Th2 polarization in mice leading to the exacerbation of airway inflammation

Assessing Estrogenic Activity of Pyrethroid Insecticides Using In Vitro Combination Assays

C2C12 myoblastoma cell differentiation and proliferation is stimulated by androgens and associated with a modulation of myostatin and Pax7 expression

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