P-glycoprotein (P-gp/MDR1)-Mediated Efflux of Sex-Steroid Hormones and Modulation of P-gp Expression In Vitro

Kim, Winnie Y.; Benet, Leslie Z.

doi:10.1023/b:pham.0000033017.52484.81

Cited by 139 publications

(92 citation statements)

References 29 publications

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“…Progesterone was found not to be transported by P-gp (34,45). It has been Future studies will require direct assay of BPA to further explore the mechanisms by which this agent interferes with P-gp and transverses the placenta.…”

Section: Discussionmentioning

confidence: 95%

Effect of bisphenol A on drug efflux in BeWo, a human trophoblast-like cell line

Audus

2005

Placenta

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. (2005) Effect of bisphenol A on drug efflux in BeWo, a human trophoblast-like cell line. Placenta, 26 Suppl.A, S96-S103. PMID: 15837075. Publisher's official version: http://dx.doi.org/10.1016/j.placenta. Keywords:Bisphenol A (BPA), P-glycoprotein (P-gp), BeWo cells, Drug efflux and 17β-estradiol (E2) Abstract:Bisphenol A (BPA) is a monomer of polycarbonate plastics that has estrogenic activities and has been shown to be a substrate for multidrug resistant efflux mechanisms, specifically, P-glycoprotein. Since the natural hormone estrogen reverses multidrug resistance in some cell types, we hypothesized that BPA might have a similar activity in trophoblasts. We have used BeWo cells as an in vitro model for human trophoblasts and calcein AM as a substrate for drug efflux mechanism to characterize BPA interactions with placental P-glycoprotein. We found that chronic exposure of BeWo cells to BPA did not alter intracellular calcein accumulation in a fashion that would be reflective of changes in Pglycoprotein expression. However, BeWo cells acutely exposed to BPA pre-treatment were observed to have a significantly decreased calcein accumulation suggesting a direct stimulatory effect on P-gp. Addition of cyclosporin A, a P-glycoprotein inhibitor and substrate, completely reversed BPA's effects on calcein accumulation and resulted in a net increase, relative to controls, in calcein accumulation by the BeWo cells. BPA was found not stimulate P-gp ATPase. Therefore, our results suggested that BPA stimulated drug efflux by BeWo cells probably by direct effects on P-glycoprotein.

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Section: Discussionmentioning

confidence: 95%

Effect of bisphenol A on drug efflux in BeWo, a human trophoblast-like cell line

Audus

2005

Placenta

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“…For example, unfavorable tumor features such as a higher frequency of being multifocal, high grade, and lymphatic involvement characterizes breast cancer in young women (Fredholm et al, 2009). Moreover, it is well-known that steroids such as estrogen and progesterone can increase the protein levels of the ABCB1 gene and function as substrates for the MDR1 protein (Kim and Benet, 2004;Coles et al, 2009). This partially explains the differential association between 3435 C/T polymorphisms and breast cancer in our study ac-cording to menopausal status and molecular subtype.…”

Section: Discussionmentioning

confidence: 99%

1236 C/T and 3435 C/T polymorphisms of the ABCB1 gene in Mexican breast cancer patients

et al. 2015

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ABSTRACT. MDR1, which is encoded by the ABCB1 gene, is involved in multidrug resistance (hydrophobic), as well as the elimination of xenotoxic agents. The association between ABCB1 gene polymorphisms ABCB1 polymorphisms in Mexican women with breast cancer and breast cancer risk in different populations has been described previously; however, the results have been inconclusive. In this study, we examined the association between polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene and breast cancer development in Mexican women according to their menopausal status and molecular classification. Molecular subtypes as well as allele and genotype frequencies were analyzed. A total of 248 women with initial breast cancer diagnosis and 180 ethnically matched, healthy, unrelated individuals were enrolled. Polymerase chain reaction-restriction fragment length polymorphism was performed to detect polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene. Premenopausal T allele carriers of the 3435 C/T polymorphism showed a 2-fold increased risk of breast cancer with respect to the reference and postmenopausal groups, as well as triplenegative expression regarding the luminal A/B molecular subrogated subtypes. In contrast, the CT genotype of the 1236 polymorphism was a protective factor against breast cancer. We conclude that the T allele carrier of the 3435 C/T polymorphism in the ABCB1 gene in combination with an estrogen receptor-negative status may be an important risk factor for breast cancer development in premenopausal women.

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“…However, it is also worth mentioning that several steroid hormones and hormone metabolites have been shown to be transported substrates of these proteins. ABCB1 was indicated to transport progesterone and aldosterone (Kim & Benet, 2004;Ueda et al, 1992), while ABCG2 is an efficient transporter for hormone derivatives, including estradiol sulfate and estradiol glucuronide (Suzuki, Suzuki, Sugimoto, & Sugiyama, 2003).…”

Section: P0170mentioning

confidence: 99%

Lipid Regulation of the ABCB1 and ABCG2 Multidrug Transporters

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Telbisz

Hegedüs

et al. 2015

Advances in Cancer Research

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P-glycoprotein (P-gp/MDR1)-Mediated Efflux of Sex-Steroid Hormones and Modulation of P-gp Expression In Vitro

Cited by 139 publications

References 29 publications

Effect of bisphenol A on drug efflux in BeWo, a human trophoblast-like cell line

Effect of bisphenol A on drug efflux in BeWo, a human trophoblast-like cell line

1236 C/T and 3435 C/T polymorphisms of the ABCB1 gene in Mexican breast cancer patients

Lipid Regulation of the ABCB1 and ABCG2 Multidrug Transporters

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