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2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Environmental Antiestrogens:Characterization and Mechanism of Action
Published in Rajesh K. Naz, Endocrine Disruptors, 2004
TCDD and related compounds inhibit growth of ER-independent pancreatic and prostate cancer cell lines, and in the former cells, this was associated with upregulation of p21 expression.145,146 In parallel studies, AhR expression and function has been investigated in several ER-negative breast cancer cell lines. Results illustrated in Figure 8.5 show that TCDD induces AhR-dependent ethoxyresorufin O-deethylase activity in MDA-MB-157, MDA-MB-436, MDA-MB-134, BT-20, MDA-MB-453, BT-474, MDA-MB-435, and HCC-38 cells, and in parallel studies, TCDD and related compounds also inhibited proliferation of these ER-negative breast cancer cell lines. However, the mechanisms of TCDD-induced growth inhibition are not related to modulation of p21, other cell cycle regulated genes, or kinase activities, and current studies are investigating other potential AhR-dependent pathways that influence ER-negative breast cancer cell proliferation.
The Association of RGS2 and Slug in the Androgen-induced Acquisition of Mesenchymal Features of Breast MDA-MB-453 Cancer Cells
Published in Endocrine Research, 2022
Dana B. Alsafadi, Mohammad S. Abdullah, Randa Bawadi, Mamoun Ahram
Slug has mainly been studied in several human cancers in relation to EMT where it has been shown to mediate AR-induced EMT not only in prostate cancer but also in bladder cancer.27 In prostate cancer, DHT treatment leads to a noticeable stimulation of Slug mRNA and protein in a dose-dependent manner 2 hours following treatment with DHT, suggesting direct transcriptional control.26,35 On the other hand, DHT stimulated Slug expression 3 days following treatment in bladder cancer.27 Unfortunately, the latter study did not examine the effect of DHT at shorter durations of exposure. In MDA-MB-453 cells, exposure of cells to DHT for 16–64 hours, but not up to 4 hours, is enough to increase expression of Slug protein as shown herein. The DHT-induced increase of Slug appears to be via transcriptional regulation since we have found three putative full ARE sites with a complete match to classic sequences within the promoter region of Slug. This finding is in agreement with the In silico analysis performed by Voutsadakis who reported the existence of several putative AREs.36 Other studies have also reported the existence of AREs in the promoter region of slug.37–39 However, none of them presented experimental proof and they all, including ours, differed in the exact location and sequenceof these AREs. Nevertheless, these results strongly suggest that AR transcriptionally directly regulates the expression of slug.
Dark Sweet Cherry (Prunus avium) Phenolics Enriched in Anthocyanins Induced Apoptosis in MDA-MB-453 Breast Cancer Cells through MAPK-Dependent Signaling and Reduced Invasion via Akt and PLCγ-1 Downregulation
Published in Nutrition and Cancer, 2021
Marjorie Anne A. Layosa, Nara N. Lage, Boon P. Chew, Liezl Atienza, Susanne Mertens-Talcott, Stephen Talcott, Giuliana D. Noratto
The MDA-MB-453 breast cell line derived from metastatic site was purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA). Cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) (4.5 g/L glucose and L-glutamine, without sodium pyruvate and HEPES) supplemented with 10% (v/v) fetal bovine serum (FBS) and 1% (v/v) penicillin–streptomycin antibiotic mix (ThermoFisher Scientific, Grand Island, NY, USA) and maintained at 37 °C with a humidified 5% CO2 atmosphere. For cell culture experiments, cells were treated with DMSO (controls) or WE (83 μg GAE/mL), ACN (19 μg C3G/mL), or PCN (22.5 μg PCN/mL) dissolved in DMSO. These doses inhibited cell growth by 50% (IC50) (determined by cell viability test after 48-h incubation using the resazurin In Vitro toxicology assay kit (Sigma-Aldrich, St Louis, MO, USA), following the manufacturer’s protocol). Final concentration of DMSO in culture medium was ≤ 0.2%. To inhibit ERK1/2 and p38 activation by phosphorylation, cells were treated with MEK1/2 inhibitor (U0126) or p38 inhibitor (SB203580) at 10 µM 1 h before DSC phenolic treatments.
Involvement of β-catenin in Androgen-induced Mesenchymal Transition of Breast MDA-MB-453 Cancer Cells
Published in Endocrine Research, 2021
Mamoun Ahram, Randa Bawadi, Mohammad S. Abdullah, Dana B. Alsafadi, Haneen Abaza, Sallam Abdallah, Ebtihal Mustafa
MDA-MB-453 cells are a commonly used cell-line model of MA with molecular characteristics of ER-negative breast cancer.4 We have previously reported that AR activation in MDA-MB-453 cells induces the acquisition of mesenchymal morphological features.33,34 These results suggest that DHT induces EMT in these cells. EMT is a process that involves orchestrated molecular and cellular events and pathways leading to cell migration.35 Multiple pathways have been linked to EMT in breast cancer, some of which are under the regulation of DHT/AR signaling.36,37 Unraveling the mechanisms by which DHT can activate EMT in ER-negative breast cancer may aid in treating this notorious type of breast cancer. Therefore, we aimed to investigate this phenomenon further by elucidating the dynamics of DHT-induced morphological change of MDA-MB-453 cells, the molecular mechanisms responsible for this change, and their functional significance.