Nonylphenol effects on human prostate non tumorigenic cells

Forte, Maurizio; Lorenzo, Mariana Di; Carrizzo, Albino; Valiante, Salvatore; Vecchione, Carmine; Laforgia, Vincenza; Falco, Maria De

doi:10.1016/j.tox.2016.05.024

Cited by 35 publications

(31 citation statements)

References 74 publications

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“…Indeed, perturbation of cell cycle and enhanced proliferation concomitant with genetic instability are considered as a risk factor for the development of cancer. Nonylphenol-dependent stimulation of clastogenic and mutagenic mechanisms as well as enhanced cell cycle and proliferation has been reported many times in different in vitro and in vivo models ( 31 , 39 – 41 ).…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Alkylphenol Exposure Promotes Mammary Epithelium Alterations and Transgenerational Developmental Defects, But Does Not Enhance Tumorigenic Behavior of Breast Cancer Cells

et al. 2017

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Fetal and neonatal exposure to long-chain alkylphenols has been suspected to promote breast developmental disorders and consequently to increase breast cancer risk. However, disease predisposition from developmental exposures remains unclear. In this work, human MCF-10A mammary epithelial cells were exposed in vitro to a low dose of a realistic (4-nonylphenol + 4-tert-octylphenol) mixture. Transcriptome and cell-phenotype analyses combined to functional and signaling network modeling indicated that long-chain alkylphenols triggered enhanced proliferation, migration ability, and apoptosis resistance and shed light on the underlying molecular mechanisms which involved the human estrogen receptor alpha 36 (ERα36) variant. A male mouse-inherited transgenerational model of exposure to three environmentally relevant doses of the alkylphenol mix was set up in order to determine whether and how it would impact on mammary gland architecture. Mammary glands from F3 progeny obtained after intrabuccal chronic exposure of C57BL/6J P0 pregnant mice followed by F1–F3 male inheritance displayed an altered histology which correlated with the phenotypes observed in vitro in human mammary epithelial cells. Since cellular phenotypes are similar in vivo and in vitro and involve the unique ERα36 human variant, such consequences of alkylphenol exposure could be extrapolated from mouse model to human. However, transient alkylphenol treatments combined to ERα36 overexpression in mammary epithelial cells were not sufficient to trigger tumorigenesis in xenografted Nude mice. Therefore, it remains to be determined if low-dose alkylphenol transgenerational exposure and subsequent abnormal mammary gland development could account for an increased breast cancer susceptibility.

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Section: Discussionmentioning

confidence: 99%

Low-Dose Alkylphenol Exposure Promotes Mammary Epithelium Alterations and Transgenerational Developmental Defects, But Does Not Enhance Tumorigenic Behavior of Breast Cancer Cells

et al. 2017

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“…Hormone-driven-characterized stages such as utero, infancy, childhood, puberty, and menopause are the most sensitive exposure periods [ 10 , 11 , 12 , 13 , 14 ]. Regarding carcinogenesis, recent studies have showed the relation of exposure to NP to the risk of breast cancer in women [ 15 ] and prostate cancer in men [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

The Roles of Three Types of Knowledge and Perceived Uncertainty in Explaining Risk Perception, Acceptability, and Self-Protective Response—A Case Study on Endocrine Disrupting Surfactants

Watanabe

2018

IJERPH

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The ubiquitous surfactants nonylphenol (NP) and its ethoxylates (NPEOs), which are known as endocrine disrupters, have appeared in the lists of restricted chemical substances, monitoring programs, and environmental quality standards of many countries due to their adverse effects. Recent studies have reported alarming levels of NP, as the final metabolite of NPEOs, in Vietnamese urban waters, whilst response to this issue is negligible. With the aim of addressing how the public perceives and expects to avoid the risk of endocrine disrupting surfactants (EDSs), the study tested the hypothesized roles of specific knowledge, general knowledge, and perceived uncertainty using structural equation modelling. The findings revealed that different types of knowledge played certain roles in explaining risk perception, risk acceptability, and self-protective response, which are distinguished by experience amongst the public. Evidence of the mediating role that perceived uncertainty may play in the decrease of risk perception and the increase of risk unacceptance has been provided. The insights gained from the study may help answer why the public are in favor of taking non-diet-related self-protective measures rather than changing their dietary habits, which illustrates a comparison with the basis of health belief model. The needs for building cognitive capacity amongst the public, particularly pregnant women and young mothers, and risk communication concerning endocrine disrupting contamination linked to reproductive health are highlighted.

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“…The endocrine disruptive properties of APs are of particular concern. Several studies have demonstrated the estrogenic activity of APs by mimicking 17b-estradiol in PNT1A human prostate cells, inducing cell proliferation and binding to progesterone receptor in human estrogen-sensitive MCF7 cells, triggering mitotic activity in the endometrium of rats, and inducing P450 aromatase activity in JEG-3 human placental cells (Forte et al, 2016;P erez-Albaladejo et al, 2017;Soto et al, 1991). The human placental choriocarcinoma JEG-3 cell line expresses high levels of P450 aromatase, a key enzyme in steroidogenesis.…”

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confidence: 99%

Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid Composition

Pérez-Albaladejo

Lacorte

Porte

2018

Toxicological Sciences

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Alkylphenols (APs) are a diverse class of chemicals that can cross the placental barrier and interfere with embryonic and fetal development. This work investigates the comparative toxicity, ability to inhibit aromatase activity, and to alter the lipid composition of 10 alkylphenols in the human placenta choriocarcinoma cell line JEG-3. Among the selected APs, 4dodecylphenol (DP), 4-heptylphenol (HP), and 4-cumylphenol (CP) showed the highest cytotoxicity (EC 50 : 18-65 mM). Aromatase inhibition was closely related to the hydrophobicity of APs. HP significantly induced the generation of reactive oxygen species (ROS) (43-fold), inhibited placental aromatase activity (IC 50 : 41 mM), and induced a general dose-dependent depletion of polyunsaturated lipids (10-20 mM), which were attributed to high levels of oxidative stress. In contrast, 2,4,6-tritert-butylphenol (TTBP) significantly induced the intracellular accumulation of triacylglycerides (TGs), whereas DP increased the synthesis of phosphatidylcholines (PCs) and TGs at the expense of diacylglycerides (DGs). Overall, this study evidences the different modes of action of alkylphenols in human placental JEG-3 cells, describes differential lipidomic fingerprints, and highlights DP, HP, CP, and TTBP as the ones that caused the most harmful effects.

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Nonylphenol effects on human prostate non tumorigenic cells

Cited by 35 publications

References 74 publications

Low-Dose Alkylphenol Exposure Promotes Mammary Epithelium Alterations and Transgenerational Developmental Defects, But Does Not Enhance Tumorigenic Behavior of Breast Cancer Cells

Low-Dose Alkylphenol Exposure Promotes Mammary Epithelium Alterations and Transgenerational Developmental Defects, But Does Not Enhance Tumorigenic Behavior of Breast Cancer Cells

The Roles of Three Types of Knowledge and Perceived Uncertainty in Explaining Risk Perception, Acceptability, and Self-Protective Response—A Case Study on Endocrine Disrupting Surfactants

Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid Composition

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