Estrogen-dependent changes in serum iron levels as a translator of the adverse effects of estrogen during infection: A conceptual framework

Hamad, Mawieh; Awadallah, Samir

doi:10.1016/j.mehy.2013.10.019

Cited by 10 publications

(12 citation statements)

References 57 publications

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“…This is in direct conflict with previous work, which has shown that elevated levels of E2 associate with increased FPN expression [12]. It is also in conflict with the finding that ER-α engagement downregulates hepcidin synthesis [15], that E2 increases systemic iron concentration [9,11,13], and that E2 enhances Hif-1α expression [12], which in turn downregulates hepcidin synthesis. Among the possibilities that could explain these inconsistencies is the type of cells used, differences in E2 concentration and/or exposure time as well as the type of receptor E2 engages within target cells.…”

Section: Discussionmentioning

confidence: 65%

“…In that, while ovariectomy in mammals results in decreased serum iron [9], use of oral contraceptives [10] and treatment of ovariectomized mice with E2 [11,12] results in increased serum iron levels [13]. The expression of several genes involved in iron metabolism including lactotransferrin, ceruloplasmin ferroxidase, lipocalin 2 and ferroportin [12] upregulate during uterine growth and differentiation.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, HIF-1α was reported to upregulate in ovarian cancer cell lines ES-2 and SKOV3 following treatment with E2 [14]. E2 has also been shown to downregulate hepcidin gene expression by binding to E2 response elements (EREs) in the hepcidin gene [13,15]; an effect that could be reversed by ICI 182780 (an E2 antagonist) [15]. E2 was also reported to inhibit the synthesis of IL-1 and IL-6 [16]; both of which are known to upregulate hepcidin gene expression as noted previously [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…Treated cells were assessed for intracellular labile iron content and the expression of several proteins involved in intracellular iron management along with cell viability. Should E2 treatment proves capable of manipulating intracellular labile iron content, it could shed more light on the anti-carcinogenic [37][38][39] and anti-inflammatory [13] potential of E2.…”

Section: Introductionmentioning

confidence: 99%

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Estrogen-Dependent Downregulation of Hepcidin Synthesis Induces Intracellular Iron Efflux in Cancer Cells In Vitro

Shafarin¹,

Bajbouj²,

Serafy³

et al. 2016

Biol Med (Aligarh)

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It is well accepted that intracellular iron overload that associate with various forms of cancer fuels tumor mutagenesis and growth. Hence, iron chelation therapy is being increasingly used to minimize iron overload in cancer patients despite significant safety and efficacy concerns. Mounting evidence suggests that estrogen (E2) downregulates hepcidin synthesis and increases serum iron concentration. It is postulated therefore that, by downregulating hepcidin synthesis, E2 may maintain ferroportin integrity and enhance intracellular iron efflux. Here, MCF-7 and SKOV-3 cancer cells treated with increasing concentrations (5, 10 and 20 nM) of E2 were assessed for intracellular labile iron content, the expression of hepcidin, ferroportin, and transferrin receptors 1 and 2 along with cell viability at different time points post treatment. In MCF-7 cells, E2 treatment resulted in a significant reduction in hepcidin synthesis, most noticeably at the 20 nM/24 h dose, a significant increase in ferroportin expression and a marked decrease in transferrin receptors 1 and 2 expression. E2-treated cells also showed reduced intracellular labile iron content most evidently at 20 nM/48 h dose and reduced viability especially at 20 nM/72 h dose. E2-treated SKOV-3 showed slightly reduced intracellular labile iron content, reduced expression of hepcidin and significantly increased expression of TFR1 but not TFR2; FPN expression was overall similar to that of controls. The effects of E2 on intracellular iron metabolism in SKOV-3 were most evident at 5 nM/24 h dose. These findings suggest that E2 treatment induces intracellular iron efflux, which may minimize intracellular iron overload in cancer cells; disrupted expression of transferrin receptor 1 and/or 2 may help sustain a low intracellular iron environment.

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Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Estrogen-Dependent Downregulation of Hepcidin Synthesis Induces Intracellular Iron Efflux in Cancer Cells In Vitro

Shafarin¹,

Bajbouj²,

Serafy³

et al. 2016

Biol Med (Aligarh)

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the FRT, estrogens induce the temporally coordinated expression of genes related with iron homeostasis, such as the iron delivery and exporter proteins, lactotransferrin (LTF), lipocalin-2 (LCN2) and FPN, respectively. By contrast, hormone action in macrophages has been poorly investigated, with some contrasting results depending on the specific macrophage population analyzed (Campesi et al, 2012;Hamad and Awadallah, 2013;Pentecost and Teng, 1987;Huang et al, 1999;Pepe, Braga, et al, 2017;Qian et al, 2015;Stuckey et al, 2006;Yang et al, 2012).…”

Section: Iron Homeostasismentioning

confidence: 99%