| 1. |
- Bajbouj, Khuloud, et al.
(författare)
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Elevated Levels of Estrogen Suppress Hepcidin Synthesis and Enhance Serum Iron Availability in Premenopausal Women
- 2018
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Ingår i: Experimental and clinical endocrinology & diabetes. - : Georg Thieme Verlag KG. - 0947-7349 .- 1439-3646. ; 126:07, s. 453-459
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Tidskriftsartikel (refereegranskat)abstract
- Clinical and experimental observations have long suggested that elevated levels of estrogen associate with increased serum iron availability. Additionally, recent work has shown that estrogen can downregulate hepcidin synthesis in vitro. This study aims at assessing whether the ability of estrogen to downregulate hepcidin synthesis translates into changes in serum iron status. Hepcidin synthesis was evaluated in MCF-7, Hep-G2 and SKOV-3 cells treated with increasing concentrations of estrogen and cultured for up to 24 h post treatment. The correlation between levels of serum estrogen, hepcidin and iron was assessed using serum samples collected from 153 premenopausal women at random and samples collected from 6 women at days 1, 5, 10, 16, 21 and 28 of the monthly cycle. Estrogen-treated MCF-7 cells showed a significant reduction in hepcidin synthesis, especially at 20 nM/24 h E2 treatment. Hepcidin synthesis was also significantly reduced in Hep-G2 and SKOV-3 cells at 20 nM/24 h E2 treatment. In serum samples collected at random, estrogen (P=0.022; R=-0.213) and iron (P=0.028; R=-0.316) correlated negatively with hepcidin and positively with each other (P=0.033; R=0.319). An overall similar pattern was also observed in monthly cycle-timed samples. These findings suggest that elevated levels of estrogen reduce hepcidin synthesis as means of enhancing serum iron content in menstruating women.
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| 2. |
- El-Huneidi, Waseem, et al.
(författare)
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Micromeria fruticosa Induces Cell Cycle Arrest and Apoptosis in Breast and Colorectal Cancer Cells
- 2020
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Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Micromeria fruticosa (L.) Druce subs p.serpyllifolia (Lamiaceae) has been used widely in folk medicine to alleviate various ailments such as abdominal pains, diarrhea, colds, eye infections, heart disorders and wounds. A few reports have confirmed different therapeutic potentialities of its extracts, including the anti-inflammatory, gastroprotective, analgesic, antiobesity and antidiabetic activities. This study aimed to investigate the mechanistic pathway of the antiproliferative activity of the ethanolic extract ofM. fruticosaon two different cancer cell lines, namely human breast (mammary carcinoma F7 (MCF-7)) and human colorectal (human colon tumor cells (HCT-116)) cell lines. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay, Annexin V-FITC/PI, caspases 8/9 and cell cycle analyses, qRT-PCR and Western blot were used to assess the effect of M. fruticosaon cytotoxicity, apoptosis, cell cycle, cell cycle-related genes and protein expression profiles in MCF-7 and HCT-116. The extract inhibits cell proliferation in a time- and dose-dependent manner. The half-maximal inhibitory concentration (IC50) for both cell lines was found to be 100 mu g/mL. Apoptosis induction was confirmed by Annexin V-FITC/PI, that was related to caspases 8 and 9 activities induction. Furthermore, the cell cycle analysis revealed arrest at G2/M phase. The underlying mechanism involved in the G2/M arrest was found to be associated with the downregulation of CDK1, cyclin B1 and survivin that was confirmed by qRT-PCR and Western blotting.
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| 3. |
- Shafarin, Jasmin, et al.
(författare)
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Estrogen-Dependent Downregulation of Hepcidin Synthesis Induces Intracellular Iron Efflux in Cancer Cells In Vitro
- 2016
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Ingår i: Biology and Medicine. - Brussels, Belgium : Longdom Group SA. - 0974-8369. ; 08:07
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- It is well accepted that intracellular iron overload that associate with various forms of cancer fuels tumormutagenesis and growth. Hence, iron chelation therapy is being increasingly used to minimize iron overload incancer 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, bydownregulating 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 forintracellular labile iron content, the expression of hepcidin, ferroportin, and transferrin receptors 1 and 2 along withcell viability at different time points post treatment. In MCF-7 cells, E2 treatment resulted in a significant reduction inhepcidin synthesis, most noticeably at the 20 nM/24 h dose, a significant increase in ferroportin expression and amarked decrease in transferrin receptors 1 and 2 expression. E2-treated cells also showed reduced intracellularlabile iron content most evidently at 20 nM/48 h dose and reduced viability especially at 20 nM/72 h dose. E2-treatedSKOV-3 showed slightly reduced intracellular labile iron content, reduced expression of hepcidin and significantlyincreased expression of TFR1 but not TFR2; FPN expression was overall similar to that of controls. The effects ofE2 on intracellular iron metabolism in SKOV-3 were most evident at 5 nM/24 h dose. These findings suggest that E2treatment induces intracellular iron efflux, which may minimize intracellular iron overload in cancer cells; disruptedexpression of transferrin receptor 1 and/or 2 may help sustain a low intracellular iron environment.
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| 4. |
- Taneera, Jalal, et al.
(författare)
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Reduced Expression of Chl1 gene Impairs Insulin Secretion by Down-Regulating the Expression of Key Molecules of β-cell Function
- 2021
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Ingår i: Experimental and Clinical Endocrinology and Diabetes. - : Georg Thieme Verlag KG. - 0947-7349 .- 1439-3646. ; 129:12, s. 864-872
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Tidskriftsartikel (refereegranskat)abstract
- Silencing of Chl1 gene expression has been previously reported to reduce insulin secretion. Nevertheless, the mechanism underlying this effect remains unclear. In this study, we performed a serial of studies to investigate how Chl1 affects insulin secretion in INS-1 cells. RNA-sequencing was used to investigate the expression of CHL1 in human adipose, liver, muscle, and human islets. Silencing of Chl1 in INS-1 cells was done to assess its impact on the insulin secretion, content, cell viability, and apoptosis. In addition, gene set enrichment analysis (GSEA) was performed to identify possible molecular signatures that associate with Chl1 expression silencing. RNA sequencing data revealed a high expression of CHL1 in pancreatic islets and adipose tissues compared to liver and muscles tissues. Diabetic islets exhibited a lower expression of CHL1 as compared to non-diabetic islets. CHL1 expression was found to correlate positively with insulin secretory index, GLP1R but inversely with HbA 1cand BMI. Silencing of Chl1 in INS-1 cells markedly reduced insulin content and secretion. The expression of key molecules of β-cell function including Insulin, Pdx1, Gck, Glut2, and Insrβ was down-regulated in Chl1 -silenced cells at transcriptional and translational levels. Cell viability, apoptosis, and proliferation rate were not affected. GSEA showed that the insulin-signaling pathway was influenced in Chl1 -silenced cells. Silencing of Chl1 impairs β-cell function by disrupting the activity of key signaling pathways of importance for insulin biosynthesis and secretion.
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