Combinatory estrogenic effects between the isoflavone genistein and the mycotoxins zearalenone and alternariol in vitro

Vejdovszky, Katharina; Schmidt, Verena; Warth, Benedikt; Marko, Doris

doi:10.1002/mnfr.201600526

Cited by 51 publications

(52 citation statements)

References 35 publications

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“…Recently, we have shown another estrogenic mycotoxin, alternariol, to potentiate estrogenic effects of Fusarium toxins in vitro ( 8 ). But also the soy isoflavone genistein, a well-described phytoestrogen, was found to interact synergistically with zearalenone in an ER-dependent reporter gene assay ( 9 ). Of consequence, it seems to be of fundamental importance for risk assessment to investigate further potential interactions between xenoestrogens in food.…”

Section: Introductionmentioning

confidence: 99%

The Hop Polyphenols Xanthohumol and 8-Prenyl-Naringenin Antagonize the Estrogenic Effects of Fusarium Mycotoxins in Human Endometrial Cancer Cells

2018

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The Fusarium toxin zearalenone (ZEN) and its reductive metabolite α-zearalenol (α-ZEL) are well-documented endocrine disruptors that are frequently found to contaminate cereal products, including beer. But also hop is known to represent a source for endocrine active compounds, containing amongst others xanthohumol (XAN), which might be converted to the potent phytoestrogen 8-prenylnaringenin (8-PN). In the present study, we investigated the interaction of these xenoestrogens in mixtures which might occur in beer. Estrogenicity was measured as induction of alkaline phosphatase (AlP) expression in estrogen-sensitive Ishikawa cells. In binary combinations, XAN was found to act as a potent antagonist of mycotoxin-induced estrogenicity, significantly suppressing the AlP-inducing impact of both ZEN and α-ZEL at nanomolar concentrations. Also 8-PN antagonized the estrogenic stimulus of the two fungal metabolites, although less pronounced. These effects also manifested in combinations of three or four test compounds, and at the level of cell proliferation, that was assessed via an E-screen-like approach in Ishikawa cells. Of note, co-exposure to the investigated myco- and phyto-estrogens did not result in additive or overadditive/synergistic estrogenic effects in the applied test system. Being aware that the actual study is still limited to the in vitro situation, our results even suggest that prenylated chalkones from hops might protect against Fusarium toxin–induced endocrine disruptive activities at concentrations that can be reached by moderate beer consumption.

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Section: Introductionmentioning

confidence: 99%

The Hop Polyphenols Xanthohumol and 8-Prenyl-Naringenin Antagonize the Estrogenic Effects of Fusarium Mycotoxins in Human Endometrial Cancer Cells

2018

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“…One urine sample contained only one mycotoxin, while 20 combinations of two or up to seven mycotoxin urinary biomarkers were observed; more than 70% of the urines contained ve or more different mycotoxins. Complex mixture toxicology remains poorly examined though several groups have recently examined combined effects in vitro [47,48,49,50,51,52,53,54,55,56,57,44,45], with animal studies being more limited [58,59]. These studies remain hard to interpret for public health decisions, but some suggest more than additive effects, thus the mixtures reported here and elsewhere highlight signi cant knowledge gaps.…”

Section: Discussionmentioning

confidence: 95%

“…However, the extremely high detection rate of 82% for total ZEN is somehow worrisome given the high xenoestrogenic potential of ZEN and its phase I biotransformation products [43]. Recent studies further highlighted that ZEN is prone to synergistic mixture effects [44,45] and able to pass the placental barrier and thus exposure of mothers is likely to result in in utero exposure of the unborn child [46]. The impact of this chronic low-dose exposures on the endocrine system and related disease should be investigated in future studies.…”

Section: Discussionmentioning

confidence: 99%

Assessment of urinary biomarkers of mycotoxin exposure in adults from Cameroon

Abia

Tchana

Djonabaye

et al. 2020

Preprint

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Background In Cameroon dietary staples are contaminated with diverse toxic fungal metabolites, known as mycotoxins. Aflatoxins and fumonisins are of particular public health concern, particularly in relation to cancer and/or early life stunting. Mixtures of these toxins are predicted from food measures, and in this work, the levels and frequencies of urinary mycotoxin biomarkers are reported in Cameroonian adults. Methods A single first void urine sample was collected from 89 adults (aged range: 28–85, male 39, female 50) from the city of Yaoundé, Centre Region, Cameroon. Urines were tested for eight distinct mycotoxins using measures of both parent compounds and/or their metabolites by Liquid Chromatography tandem mass spectrometry (LC-MS/MS). Results Altogether seven distinct mycotoxins, aflatoxin, fumonisin, deoxynivalenol, zearalenone, nivalenol, ochratoxin A and citrinin, (or their metabolites) were observed in urine samples. At least one mycotoxin was detected in all of the urine samples, 87 (97.8%) of which were above the method’s quantification limit. Aflatoxin M1 was detected in 42% (n.d. − 0.21 µg L− 1) of samples of which about a quarter additionally contained fumonisin B1. Of the remaining toxins deoxynivalenol, zearalenone, ochratoxin A, nivalenol and citrinin were present in 78%, 99% 95%, 53%, and 87% of the samples respectively. Alternariol was not detected in any sample. Mixtures of mycotoxins in the samples were frequently observed with 64 samples (72%) containing more than five mycotoxins. Estimates of intake exceeded the TDIs for fumonisin (n = 4), deoxynivalenol (n = 1) and zearalenone (n = 2), no TDI is set for aflatoxin. Conclusions This study reveals frequent co-exposure of Cameroonian individuals to a complex mixture of toxic and carcinogenic mycotoxins, with mixtures of aflatoxin and fumonisin a particular priority from a public health standpoint.

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“…After 48 h cells were either incubated with common medium as control, PAL (200 nM), LET (10 nM), a PAL+LET combination (200 nM, 10 nM), or the combined treatment plus the phytoestrogen GEN (1 µM) or the mycoestrogen ZEN (100 nM) for 48 h. The drug concentrations were based on a realistic ratio and previous reports (Finn et al (2009), Johnson et al in preparation). For xenoestrogens, realistic concentrations were also in line with published data on food consumption/contamination and background concentrations in bio-fluids (Vejdovszky et al, 2017; Warth et al, 2013) were chosen to mimic a scenario as realistic as possible. For the duration of T47D experiments, phenol red-free RPMI 1640 and charcoal-dextran stripped FBS were used as well.…”

Section: Star Methodsmentioning

confidence: 99%

Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy

Warth

Raffeiner

Granados

et al. 2017

Preprint

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HighlightsSynergism of combined palbociclib/letrozole chemotherapy was examined by global metabolomicsCombination therapy led to more pronounced effects on the MCF-7 metabolome than single agentsDietary phyto- and mycoestrogens significantly affected the metabolic and anti-oncogenic response of the drugsImplications of these bio-active chemicals on therapeutic success in breast cancer patients appear plausibleIn BriefWarth et al. used innovative global metabolomics and pathway prediction technology to describe the metabolic effects of the combined palbociclib/letrozole breast cancer therapy. Moreover, the role of dietary xenoestrogens on this treatment was examined by metabolite data, proliferation experiments, and functional assays.SummaryRecently, the palbociclib/letrozole combination therapy was granted accelerated FDA approval for the treatment of estrogen receptor (ER) positive breast cancer. Since the underlying metabolic effects of these drugs are yet unknown, we investigated their synergism at the metabolome level in MCF-7 cells. As xenoestrogens interact with the ER, we additionally aimed at deciphering the impact of the phytoestrogen genistein, and the estrogenic mycotoxin zearalenone on this treatment. A global metabolomics approach was applied to unravel metabolite and pathway modifications. The results clearly showed that the combined effects of palbociclib and letrozole on cellular metabolism were far more pronounced than that of each agent alone and potently influenced by xenoestrogens. This behavior was confirmed in proliferation experiments and functional assays. Specifically, amino acids and central carbon metabolites were attenuated while higher abundances were observed for fatty acids and most nucleic acid related metabolites. Interestingly, exposure to model xenoestrogens appeared to partially counteract these effects.

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Combinatory estrogenic effects between the isoflavone genistein and the mycotoxins zearalenone and alternariol in vitro

Cited by 51 publications

References 35 publications

The Hop Polyphenols Xanthohumol and 8-Prenyl-Naringenin Antagonize the Estrogenic Effects of Fusarium Mycotoxins in Human Endometrial Cancer Cells

The Hop Polyphenols Xanthohumol and 8-Prenyl-Naringenin Antagonize the Estrogenic Effects of Fusarium Mycotoxins in Human Endometrial Cancer Cells

Assessment of urinary biomarkers of mycotoxin exposure in adults from Cameroon

Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy

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