Use of reporter cell lines for detection of endocrine-disrupter activity

Willemsen, P.; Scippo, Marie‐Louise; Kausel, Gudrun; Figueroa, Jaime; Maghuin‐Rogister, Guy; Martial, Joseph; Müller, Marc

doi:10.1007/s00216-003-2217-2

Cited by 82 publications

(9 citation statements)

References 45 publications

(40 reference statements)

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“…Screening for other hormonal activities has received less attention. Luteolin exhibits weak androgen antagonist activity [42] as does apigenin, a flavone closely related to luteolin [42, 43]. Apigenin binds to progesterone receptors though, curiously, binding by luteolin was not detected [44].…”

Section: Discussionmentioning

confidence: 99%

“…Apigenin binds to progesterone receptors though, curiously, binding by luteolin was not detected [44]. Apigenin has been reported to possess progestational activity [45, 46] or both progestin agonist and antagonist activity [43]. Apigenin inhibits the growth of progestin-dependent tumor models in vivo consistent with progesterone antagonist activity [47, 48].…”

Section: Discussionmentioning

confidence: 99%

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Endocrine Disrupting Activities of the Flavonoid Nutraceuticals Luteolin and Quercetin

et al. 2013

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Dietary plant flavonoids have been proposed to contribute to cancer prevention, neuroprotection, and cardiovascular health through their anti-oxidant, anti-inflammatory, pro-apoptotic, and antiproliferative activities. As a consequence, flavonoid supplements are aggressively marketed by the nutraceutical industry for many purposes, including pediatric applications, despite inadequate understanding of their value and drawbacks. We show that two flavonoids, luteolin and quercetin, are promiscuous endocrine disruptors. These flavonoids display progesterone antagonist activity beneficial in a breast cancer model but deleterious in an endometrial cancer model. Concurrently, luteolin possesses potent estrogen agonist activity while quercetin is considerably less effective. These results highlight the promise and peril of flavonoid nutraceuticals and suggest caution in supplementation beyond levels attained in a healthy, plant-rich diet.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Endocrine Disrupting Activities of the Flavonoid Nutraceuticals Luteolin and Quercetin

et al. 2013

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“…Four reporter gene cell lines were previously developed by transforming human mammary gland cell lines with the luciferase gene under the control of a steroid hormone inducible promotor as described in Willemsen et al 26 The TARM-Luc cell line is specific for the detection of androgens and progestagens, MMV-Luc cell line for oestrogens, TM-Luc for progestagens and TGRM-Luc for glucocorticoids and progestogens. 27 These transformed cell lines were routinely cultured in cell culture medium containing DMEM and 10% foetal bovine serum.…”

Section: Reporter Gene Assays (Rga's)mentioning

confidence: 99%

Improvements in single‐use bioreactor film material composition leads to robust and reliable Chinese hamster ovary cell performance

Kelly

Dorival-García

Paré

et al. 2019

Biotechnology Progress

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Single‐use technologies, in particular disposable bioreactor bags, have become integral within the biopharmaceutical community. However, safety concerns arose upon the identification of toxic leachable compounds derived from the plastic materials. Although the leachable bis(2,4‐di‐tert‐butylphenyl)‐phosphate (bDtBPP) has been previously shown to inhibit CHO cell growth, it is critical to determine if other compounds like this are still present in subsequent generations of films for industrial application. This study compares the performance of CHO cells, CHO‐K1, and CHO‐DP12, cultured in media conditioned in an older single‐use bioreactor (SUB) film (F‐1) and a newer generation film (F‐2) from the same vendor. CHO cells cultured in media conditioned for 7 days in the F‐1 film demonstrated significantly reduced growth and antibody productivity profiles when compared to controls and media conditioned for the same time period in the newer F‐2 film. Proteomic profiling of CHO cells cultured in the F‐1 conditioned media identified differentially expressed proteins involved in oxidative stress response as well as compromised ATP synthesis. These potentially metabolically compromised cells exhibited reduced oxidative phosphorylation activity as well as lower glycolytic metabolism, characteristic of slower growing cells. Nonvolatile and metal leachables analysis of film extracts by LC–MS revealed a reduction in the abundance of the analyzed leachates from F‐2 films when compared to F‐1 films including bDtBPP, potentially explaining improved CHO cell growth in F‐2 conditioned media. Furthermore, in vitro endocrine disruptor testing of the known leachable revealed this molecule to possess the potential to act as an androgen antagonist. This study demonstrates an improvement in the materials composition used in modern generations of SUBs for safe application in the bioprocess.

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“…More functionally, Willemsen et al (2003) produced cell lines to identify novel steroid receptors and identified apigenin as a weak PR agonist. In Ishikawa cells, apigenin antagonized progesterone stimulated SLUTE1 expression with an EC 50 of 850 nM.…”

Section: Phytoprogestinsmentioning

confidence: 99%

Phytosteroids beyond estrogens: Regulators of reproductive and endocrine function in natural products

Dean¹,

Murphy²,

Burdette³

2017

Molecular and Cellular Endocrinology

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Foods and botanical supplements can interfere with the endocrine system through the presence of phytosteroids – chemicals that interact with steroids receptors. Phytoestrogens are well studied, but compounds such as kaempferol, apigenin, genistein, ginsenoside Rf, and glycyrrhetinic acid have been shown to interact with non-estrogen nuclear receptors. These compounds can have agonist, antagonist, or mixed agonist/antagonist activity depending on compound, receptor, cell line or tissue, and concentration. Some phytosteroids have also been shown to inhibit steroid metabolizing enzymes, resulting in biological effects through altered endogenous steroid concentrations. An interesting example, compound A (4-[1-chloro-2-(methylamino)ethyl]phenyl acetate hydrochloride (1:1)) is a promising selective glucocorticoid receptor modulator (SGRM) based on a phytosteroid isolated from Salsola tuberculatiformis Botschantzev. Given that $6.9 billion of herbal supplements are sold each year, is clear that further identification and characterization of phytosteroids is needed to ensure the safe and effective use of botanical supplements.

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Use of reporter cell lines for detection of endocrine-disrupter activity

Cited by 82 publications

References 45 publications

Endocrine Disrupting Activities of the Flavonoid Nutraceuticals Luteolin and Quercetin

Endocrine Disrupting Activities of the Flavonoid Nutraceuticals Luteolin and Quercetin

Improvements in single‐use bioreactor film material composition leads to robust and reliable Chinese hamster ovary cell performance

Phytosteroids beyond estrogens: Regulators of reproductive and endocrine function in natural products

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