scholarly journals Study of danazol active agent effect on Mcf10a breast cells redox phosphorylation

2021 ◽  
Vol 60 (2) ◽  
pp. 32-35
Author(s):  
B. G. Yeszhan ◽  
S. O. Ossikbayeva
Keyword(s):  
Molecular Mechanisms ◽  
Active Agent ◽  
Cyst Formation ◽  
Cell Membrane Permeability ◽  
Mcf10a Cell ◽  
Respiratory Complex ◽  
Fibrocystic Mastopathy ◽  
Cell Energy ◽  
Breast Cells ◽  
Energy Center

Relevance: Fibrocystic mastopathy is one of the most complex breast pathologies, occurring in about 60% of women. The causes and molecular mechanisms of cyst formation in fibrocystic mastopathy are not fully understood, and effective treatment methods are not widely implemented. However, there is evidence of the fibrocystic mastopathy malignization risk. We studied the molecular effect of the active agent danazol on the respiratory complex in mitochondria, which occur in various concentrations and are considered the cell energy center. A method of permeation with special substances was developed to improve the cell membrane permeability in the intracellular proteins and nucleic acids analysis. The scientists aimed to study the Mcf10a cell line mitochondrial respiratory complex using the permeabilization method. Purpose: To study the effect of different danazol concentrations on Mcf10a breast cells redox phosphorylation in women with fibrocystic mastopathy. Results: Monitoring the redox phosphorylation process using the respiratory complex substrates affecting the Msf10A breast cells respiratory chain showed the danazol 30 μM effect on the respiratory complex I. Conclusions: According to oxygraphic records, 10 minutes’ exposure to danazol 30 μM after permeabilization with digitonin increased the Msf10A cells’ oxidative phosphorylation compared with the control. The respiratory rate decreased by 45% ten minutes after treatment with digitonin.

scholarly journals Study of danazol active agent effect on Mcf10a breast cells redox phosphorylation

2021 ◽  
Vol 60 (2) ◽  
pp. 32-35
Author(s):  
B. G. Yeszhan ◽  
S. O. Ossikbayeva
Keyword(s):  
Molecular Mechanisms ◽  
Active Agent ◽  
Cyst Formation ◽  
Cell Membrane Permeability ◽  
Mcf10a Cell ◽  
Respiratory Complex ◽  
Fibrocystic Mastopathy ◽  
Cell Energy ◽  
Breast Cells ◽  
Energy Center

Fibrocystic mastopathy is one of the most complex breast pathologies, occurring in about 60% of women. The causes and molecular mechanisms of cyst formation in fibrocystic mastopathy are not fully understood, and effective treatment methods are not widely implemented. However, there is evidence of the fibrocystic mastopathy malignization risk. We studied the molecular effect of the active agent danazol on the respiratory complex in mitochondria, which occur in various concentrations and are considered the cell energy center. A method of permeation with special agents was developed to improve the cell membrane permeability in the intracellular proteins and nucleic acids analysis. The scientists aimed to study the Mcf10a cell line mitochondrial respiratory complex using the permeabilization method. Purpose: To study the effect of different danazol concentrations on Mcf10a breast cells redox phosphorylation in women with fibrocystic mastopathy. Results: Monitoring the redox phosphorylation process using complex respiratory substrates affecting the Msf10A breast cells respiratory chain showed the danazol 30 μM effect on the respiratory complex I. Conclusions: According to oxygraphic records, 10 minutes’ exposure to danazol 30 μM after permeabilization with digitonin increased the Msf10A cells’ oxidative phosphorylation compared with the control. The respiratory rate decreased by 45% ten minutes after treatment with digitonin.

scholarly journals Proton-irradiated breast cells: molecular points of view

2019 ◽  
Vol 60 (4) ◽  
pp. 451-465 ◽  
Author(s):  
Valentina Bravatà ◽  
Francesco P Cammarata ◽  
Luigi Minafra ◽  
Pietro Pisciotta ◽  
Concetta Scazzone ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Fate ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Proton Irradiation ◽  
Expression Profiles ◽  
Treatment Plan ◽  
Mcf10a Cell ◽  
Specific Cell ◽  
Dose Dependent

Abstract Breast cancer (BC) is the most common cancer in women, highly heterogeneous at both the clinical and molecular level. Radiation therapy (RT) represents an efficient modality to treat localized tumor in BC care, although the choice of a unique treatment plan for all BC patients, including RT, may not be the best option. Technological advances in RT are evolving with the use of charged particle beams (i.e. protons) which, due to a more localized delivery of the radiation dose, reduce the dose administered to the heart compared with conventional RT. However, few data regarding proton-induced molecular changes are currently available. The aim of this study was to investigate and describe the production of immunological molecules and gene expression profiles induced by proton irradiation. We performed Luminex assay and cDNA microarray analyses to study the biological processes activated following irradiation with proton beams, both in the non-tumorigenic MCF10A cell line and in two tumorigenic BC cell lines, MCF7 and MDA-MB-231. The immunological signatures were dose dependent in MCF10A and MCF7 cell lines, whereas MDA-MB-231 cells show a strong pro-inflammatory profile regardless of the dose delivered. Clonogenic assay revealed different surviving fractions according to the breast cell lines analyzed. We found the involvement of genes related to cell response to proton irradiation and reported specific cell line- and dose-dependent gene signatures, able to drive cell fate after radiation exposure. Our data could represent a useful tool to better understand the molecular mechanisms elicited by proton irradiation and to predict treatment outcome

scholarly journals Stem cells and fluid flow drive cyst formation in an invertebrate excretory organ

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Hanh Thi-Kim Vu ◽  
Jochen C Rink ◽  
Sean A McKinney ◽  
Melainia McClain ◽  
Naharajan Lakshmanaperumal ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Human Kidney ◽  
Cyst Formation ◽  
Cystic Kidney ◽  
Flow Sensing ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Genetic Interference ◽  
Cystic Kidney Diseases

Cystic kidney diseases (CKDs) affect millions of people worldwide. The defining pathological features are fluid-filled cysts developing from nephric tubules due to defective flow sensing, cell proliferation and differentiation. The underlying molecular mechanisms, however, remain poorly understood, and the derived excretory systems of established invertebrate models (Caenorhabditis elegans and Drosophila melanogaster) are unsuitable to model CKDs. Systematic structure/function comparisons revealed that the combination of ultrafiltration and flow-associated filtrate modification that is central to CKD etiology is remarkably conserved between the planarian excretory system and the vertebrate nephron. Consistently, both RNA-mediated genetic interference (RNAi) of planarian orthologues of human CKD genes and inhibition of tubule flow led to tubular cystogenesis that share many features with vertebrate CKDs, suggesting deep mechanistic conservation. Our results demonstrate a common evolutionary origin of animal excretory systems and establish planarians as a novel and experimentally accessible invertebrate model for the study of human kidney pathologies.

Simulation of Operation, Energy Savings, and CO2 Balance of a Domestic Fuel Cell Energy Center

Fuel Cells ◽  
2007 ◽  
Vol 7 (3) ◽  
pp. 190-196 ◽  
Author(s):  
J. Pawlik ◽  
H. Klaschinsky ◽  
R. Dippel ◽  
M. Mlynski ◽  
A. Hlawenka ◽  
...  
Keyword(s):  
Fuel Cell ◽  
Energy Savings ◽  
Cell Energy ◽  
Co2 Balance ◽  
Energy Center ◽  
Domestic Fuel

scholarly journals Increased glucosylceramide production leads to decreased cell energy metabolism and lowered tumor marker expression in non-cancerous liver cells

2021 ◽  
Author(s):  
Marthe-Susanna Wegner ◽  
Nina Schömel ◽  
Ellen M. Olzomer ◽  
Sandra Trautmann ◽  
Catherine Olesch ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Molecular Mechanisms ◽  
Normal Liver ◽  
Liver Cells ◽  
New Therapeutic Approaches ◽  
Cell Energy ◽  
Murine Liver ◽  
Cancer Types ◽  
Cancer Phenotypes ◽  
Poor Outcomes

AbstractHepatocellular carcinoma (HCC) is one of the most difficult cancer types to treat. Liver cancer is often diagnosed at late stages and therapeutic treatment is frequently accompanied by development of multidrug resistance. This leads to poor outcomes for cancer patients. Understanding the fundamental molecular mechanisms leading to liver cancer development is crucial for developing new therapeutic approaches, which are more efficient in treating cancer. Mice with a liver specific UDP-glucose ceramide glucosyltransferase (UGCG) knockout (KO) show delayed diethylnitrosamine (DEN)-induced liver tumor growth. Accordingly, the rationale for our study was to determine whether UGCG overexpression is sufficient to drive cancer phenotypes in liver cells. We investigated the effect of UGCG overexpression (OE) on normal murine liver (NMuLi) cells. Increased UGCG expression results in decreased mitochondrial respiration and glycolysis, which is reversible by treatment with EtDO-P4, an UGCG inhibitor. Furthermore, tumor markers such as FGF21 and EPCAM are lowered following UGCG OE, which could be related to glucosylceramide (GlcCer) and lactosylceramide (LacCer) accumulation in glycosphingolipid-enriched microdomains (GEMs) and subsequently altered signaling protein phosphorylation. These cellular processes lead to decreased proliferation in NMuLi/UGCG OE cells. Our data show that increased UGCG expression itself does not induce pro-cancerous processes in normal liver cells, which indicates that increased GlcCer expression leads to different outcomes in different cancer types. Graphic abstract

scholarly journals Cellular Pharmacology of Curcumin With and Without Piperine

2021 ◽  
Author(s):  
Rama I Mahran ◽  
Pan Shu ◽  
Justin Colacino ◽  
Magda M Hagras ◽  
Duxin Sun ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cellular Uptake ◽  
Mcf10a Cell ◽  
Cellular Pharmacology ◽  
Normal Human Breast ◽  
Breast Stem Cell ◽  
Breast Cells ◽  
Normal Human ◽  
Mcf10a Cells ◽  
Mammosphere Assay

Prior reports have suggested that piperine enhances curcumin anti-carcinogenesis. We tested the hypothesis that piperine increases the intracellular concentrations of curcumin by improving intracellular uptake or reducing curcumin efflux or metabolism in breast cells. We incubated SUM149, MCF10A, primary normal human breast cells, ALDH+, and ALDH-CD44+24- SUM149 cells with curcumin with or without piperine at concentrations 1 uM to 15 uM for time periods of 15 minutes to 24 hours. We assayed cell viability by MTT assay and proliferation by primary mammosphere assay. Curcumin and its metabolites were assayed using liquid chromatography mass spectroscopy. Curcumin, but not piperine, showed significantly higher effects on the viability of breast cancer SUM149 cells than in non-tumorigenic MCF10A cells. Curcumin + piperine synergistically reduced viability of SUM149 cells but had a concentration dependent effect upon MCF10A cell viability. Cellular uptake of curcumin in SUM149 is significantly higher, while the efflux in SUM149 is significantly lower than in MCF10A, which correlated with cell viability. Piperine did not alter curcumin cellular uptake, efflux, or metabolism in any of the cell models. The observed synergism of piperine+curcumin in reducing breast stem cell self renewal is likely due to independent anti-carcinogenesis effects rather than any effects upon intracellular curcumin concentrations.

scholarly journals Poly(ADP-ribosyl)ation associated changes in CTCF-chromatin binding and gene expression in breast cells

2017 ◽  
Author(s):  
Ioanna Pavlaki ◽  
France Docquier ◽  
Igor Chernukhin ◽  
Georgia Kita ◽  
Svetlana Gretton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mass ◽  
Molecular Mechanisms ◽  
Apparent Molecular Mass ◽  
Ctcf Binding ◽  
Binding Motif ◽  
Cellular Functions ◽  
Altered Expression ◽  
Cycle Arrest ◽  
Breast Cells

AbstractCTCF is an evolutionarily conserved and ubiquitously expressed architectural protein regulating a plethora of cellular functions via different molecular mechanisms. CTCF can undergo a number of post-translational modifications which change its properties and functions. One such modifications linked to cancer is poly(ADP-ribosyl)ation (PARylation). The highly PARylated CTCF form has an apparent molecular mass of 180 kDa (referred to as CTCF180), which can be distinguished from hypo- and non-PARylated CTCF with the apparent molecular mass of 130 kDa (referred to as CTCF130). The existing data accumulated so far have been mainly related to CTCF130. However, the properties of CTCF180 are not well understood despite its abundance in a number of primary tissues. In this study we performed ChIP-seq and RNA-seq analyses in human breast cells 226LDM, which display predominantly CTCF130 when proliferating, but CTCF180 upon cell cycle arrest. We observed that in the arrested cells the majority of sites lost CTCF, whereas fewer sites gained CTCF or remain bound (i.e. common sites). The classical CTCF binding motif was found in the lost and common, but not in the gained sites. The changes in CTCF occupancies in the lost and common sites were associated with increased chromatin densities and altered expression from the neighboring genes. Based on these results we propose a model integrating the CTCF130/180 transition with CTCF-DNA binding and gene expression changes. This study also issues an important cautionary note concerning the design and interpretation of any experiments using cells and tissues where CTCF180 may be present.

cAMP-dependent chloride secretion mediates tubule enlargement and cyst formation by cultured mammalian collecting duct cells

2009 ◽  
Vol 296 (2) ◽  
pp. F446-F457 ◽  
Author(s):  
Roberto Montesano ◽  
Hafida Ghzili ◽  
Fabio Carrozzino ◽  
Bernard C. Rossier ◽  
Eric Féraille
Keyword(s):  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Collecting Duct ◽  
Fluid Secretion ◽  
Cyst Formation ◽  
Chloride Secretion ◽  
Cystic Kidney ◽  
Pcr Analysis ◽  
Renal Tubules

Polycystic kidney diseases result from disruption of the genetically defined program that controls the size and geometry of renal tubules. Cysts which frequently arise from the collecting duct (CD) result from cell proliferation and fluid secretion. From mCCDcl1 cells, a differentiated mouse CD cell line, we isolated a clonal subpopulation (mCCD-N21) that retains morphogenetic capacity. When grown in three-dimensional gels, mCCD-N21 cells formed highly organized tubular structures consisting of a palisade of polarized epithelial cells surrounding a cylindrical lumen. Subsequent addition of cAMP-elevating agents (forskolin or cholera toxin) or of membrane-permeable cAMP analogs (CPT-cAMP) resulted in rapid and progressive dilatation of existing tubules, leading to the formation of cystlike structures. When grown on filters, mCCD-N21 cells exhibited a high transepithelial resistance as well as aldosterone- and/or vasopressin-induced amiloride-sensitive and -insensitive current. The latter was in part inhibited by Na+-K+-2Cl− cotransporter (bumetanide) and chloride channel (NPPB) inhibitors. Real-time PCR analysis confirmed the expression of NKCC1, the ubiquitous Na+-K+-2Cl− cotransporter and cystic fibrosis transmembrane regulator (CFTR) in mCCD-N21 cells. Tubule enlargement and cyst formation were prevented by inhibitors of Na+-K+-2Cl− cotransporters (bumetanide or ethacrynic acid) or CFTR (NPPB or CFTR inhibitor-172). These results further support the notion that cAMP signaling plays a key role in renal cyst formation, at least in part by promoting chloride-driven fluid secretion. This new in vitro model of tubule-to-cyst conversion affords a unique opportunity for investigating the molecular mechanisms that govern the architecture of epithelial tubes, as well as for dissecting the pathophysiological processes underlying cystic kidney diseases.

scholarly journals Combined transcriptomic and lipidomic analysis reveals aberrant lipid metabolism in central nervous system hemangioblastomas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qiguang Wang ◽  
Wenke Liu ◽  
Si Zhang ◽  
Zuoyu Liang ◽  
Linhong Jiang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lipid Metabolism ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Cyst Formation ◽  
Phospholipase Activity ◽  
Lipidomic Analysis ◽  
The Central Nervous System ◽  
Altered Lipid

AbstractPeritumoral cysts are commonly detected in the central nervous system tumors, especially hemangioblastomas (HBs). However, the molecular mechanisms driving their formation and propagation are still unknown. We conducted an integrated lipidomics and transcriptomics analysis on solid and cystic HB samples in order to elucidate the changes in the lipid profile and expression of lipid metabolism-related genes during cyst formation. Transcriptomic analysis revealed differential expression of several genes between the solid and cystic HBs, and those associated with lipid metabolism, such as ADCY4, MGLL, ACOT2, DGKG, SHC1 and LPAR2, were markedly dysregulated in the cystic HBs. The lipidomic analysis further showed a significant reduction in the abundance of triacylglycerol, ceramide, lysophosphatidylcholine and lysophosphatidylethanolamine, and an increase in phosphatidylcholine and phosphatidylethanolamine levels in the cystic HBs. Furthermore, bioinformatics analysis revealed altered lipid biosynthesis, glycerophospholipid metabolism and phospholipase activity in the cystic HBs. Taken together, our findings indicate that cyst formation in HBs is related with aberrant lipid metabolism.

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