Passive permeability assay of doxorubicin through model cell membranes under cancerous and normal membrane potential conditions.

In this study, the effects of the membrane potential of breast cancer cells (-30 mV) and normal breast epithelial cells (-60 mV) on doxorubicin (DOX) permeability was studied. To achieve this goal, black lipid membranes (BLMs) as a model cell membrane were formed with DPhPC phospholipids in a single aperture of a Teflon sheet by the Montal and Mueller method. The presence of the BLM was characterized by capacitive measurements. The measured specific capacitance of 0.6 µF/cm2 after applying the Montal and Mueller method, confirming the presence of a BLM in the aperture. In addition, the very low current leakage of the BLM (9 - 24 pA) and ClyA-protein channel insertion in the BLM indicate the compactness, high quality, and thickness of 3 - 5 nm of the BLM. Afterwards, the permeability of doxorubicin through the BLM was studied at defined cell conditions (37 ℃ and pH 7.4), as well as cancerous and healthy epithelial-cell membrane potentials (-30 mV and -60 mV, respectively). The results show a slow DOX penetration within the first few hours, which increases rapidly with time. The initial slow penetration can be attributed to an electrostatic interaction between doxorubicin and DPhPC molecules in the model cell membrane. Furthermore, a MTT assay on MCF-10A and MCF-7 under different concentrations of doxorubicin confirmed that the cancerous MCF-7 cell line is more resistant to doxorubicin in comparison with the non-cancerous MCF-10A. Such studies highlight important strate...
Source: European Journal of Pharmaceutics and Biopharmaceutics - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Biopharm Source Type: research

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Publication date: Available online 12 September 2020Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Harshit Shah, Lizhi Pang, Hongzhi Wang, Dan Shu, Steven Y. Qian, Venkatachalem Sathish
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research
This study was conducted to clarify the effect of the tivantinib in regulating breast cancer therapy-resistant protein (BCRP), a key transporter of 5-fluorouracil (5-FU), and dihydropyridine dehydrogenase (DPYD), a major metabolic enzyme of 5-FU. To this end, cMET gene expression was determined by RT-PCR in HepG2 (human hepatoma) cells. The transcriptional start sites of BCRP were determined by 5'-rapid amplification of cDNA ends (5'-RACE). BCRP and DPYD mRNA levels were determined by real-time RT-PCR, and promoter activities were measured by dual-luciferase assays. Results show that hepatocyte growth factor (HGF) upregula...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research
Contributors : Zhao Zhang ; Mingjun Bi ; Zhijie LiuSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensCellular plasticity has emerged as an important mechanism of therapy resistance in cancers, yet the underlying molecular mechanisms remain unclear. Using an established breast cancer cellular model for endocrine resistance, we show that hormone resistance is associated with enhanced cellular plasticity, indicated by a general downregulation of luminal/epithelial differentiation markers and upregulation of basal/mesenchymal invasive markers. Our extensive omics studies including GRO-seq o...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Contributors : Zhao Zhang ; Mingjun Bi ; Zhijie LiuSeries Type : OtherOrganism : Homo sapiensCellular plasticity has emerged as an important mechanism of therapy resistance in cancers, yet the underlying molecular mechanisms remain unclear. Using an established breast cancer cellular model for endocrine resistance, we show that hormone resistance is associated with enhanced cellular plasticity, indicated by a general downregulation of luminal/epithelial differentiation markers and upregulation of basal/mesenchymal invasive markers. Our extensive omics studies including GRO-seq on enhancer landscapes demonstrate that the gl...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research
Contributors : Zhao Zhang ; Mingjun Bi ; Zhijie LiuSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensCellular plasticity has emerged as an important mechanism of therapy resistance in cancers, yet the underlying molecular mechanisms remain unclear. Using an established breast cancer cellular model for endocrine resistance, we show that hormone resistance is associated with enhanced cellular plasticity, indicated by a general downregulation of luminal/epithelial differentiation markers and upregulation of basal/mesenchymal invasive markers. Our extensive omics studies inclu...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research
Contributors : Zhao Zhang ; Mingjun Bi ; Zhijie LiuSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensCellular plasticity has emerged as an important mechanism of therapy resistance in cancers, yet the underlying molecular mechanisms remain unclear. Using an established breast cancer cellular model for endocrine resistance, we show that hormone resistance is associated with enhanced cellular plasticity, indicated by a general downregulation of luminal/epithelial differentiation markers and upregulation of basal/mesenchymal invasive markers. Our extensive omics studies inclu...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research
Breast cancer has become one of the most serious disease threatening mankind health in the world. Accumulating studies indicated that circRNAs played an important role in the occurrence and progression of breast cancer, however, the roles of circRNA_103809 in breast cancer progression remain unclear. Therefore, in this study, we aimed to clarify the potential role and regulatory mechanism of circRNA_103809 in the development of breast cancer. Firstly, the expression level of circRNA_103809 and microRNA-532-3p (miR-532-3p) in breast cancer tissues and normal tissues were detected with the quantitative real-time polymerase c...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusions: Taken together, a cell polarity/EMP-enriched shRNA library screen identified relevant gene products that could be targeted alongside current chemotherapeutic agents for the treatment of invasive BC.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Breast cancer depends on women’s age. Its chemotherapy and hormone therapy lead to the loss of bone density and disruption of the skeleton. The proteins RANK and RANKL play a pivotal role in the formation of osteoclasts. It is also well established that the same proteins (RANK and RANKL) are the main molecules that play an important role in mammary stem cell biology. Mammary stem cells guarantee differentiation of the epithelial mammary cells, the growth of which is regulated by the progesterone-induced RANKL signaling pathway. The crosstalk between progesterone receptor, stimulated by progesterone and its a...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
ConclusionsWe identified a stemness-related gene panel associated with JQ1 and describe how this inhibitor modifies the stemness landscape in TNBC. Therefore, we propose a novel role for JQ1 as a stemness-targeting drug. Loss of the stem cell phenotype via JQ1 treatment could lead to less aggressive and more chemo-sensitive tumours, reflecting a better patient prognosis. Thus, the identified gene panel may be of interest for the clinical management of patients with aggressive TNBC.
Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research
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