Search results for "MAC"
showing 10 items of 24950 documents
Rosmarinic Acid Activates AMPK to Inhibit Metastasis of Colorectal Cancer
2018
Rosmarinic acid (RA) has been used as an anti-inflammatory, anti-diabetic, and anti-cancer agent. Although RA has also been shown to exert an anti-metastatic effect, the mechanism of this effect has not been reported to be associated with AMP-activated protein kinase (AMPK). The aim of this study was to elucidate whether RA could inhibit the metastatic properties of colorectal cancer (CRC) cells via the phosphorylation of AMPK. RA inhibited the proliferation of CRC cells through the induction of cell cycle arrest and apoptosis. In several metastatic phenotypes of CRC cells, RA regulated epithelial–mesenchymal transition (EMT) through the upregulation of an epithelial marker, E-cadherin, and…
Epimagnolin A, a tetrahydrofurofuranoid lignan from Magnolia fargesii, reverses ABCB1-mediated drug resistance.
2018
Abstract Background Epimagnolin A is an ingredient of the Chinese crude drug Shin-i, derived from the dried flower buds of Magnolia fargesii and Magnolia flos, which has been traditionally used for the treatment of allergic rhinitis and nasal congestion, empyema, and sinusitis. The pharmacokinetic activity of epimagnolin A remains to be evaluated. Purpose In this study, we examined the possible interactions of epimagnolin A with human ATP-binding cassette (ABC) transporter ABCB1, a membrane protein vital in regulating the pharmacokinetics of drugs and xenobiotics. Study design/methods The interaction of epimagnolin A with ABCB1 was evaluated in calcein, ATPase, and MTT assays by using Flp-I…
Repurposing of Bromocriptine for Cancer Therapy
2018
Bromocriptine is an ergot alkaloid and dopamine D2 receptor agonist used to treat Parkinson’s disease, acromegaly, hyperprolactinemia, and galactorrhea, and more recently diabetes mellitus. The drug is also active against pituitary hormone-dependent tumors (prolactinomas and growth-hormone producing adenomas). We investigated, whether bromocriptine also inhibits hormone-independent and multidrug-resistant (MDR) tumors. We found that bromocriptine was cytotoxic towards drug-sensitive CCRF-CEM, multidrug-resistant CEM/ADR5000 leukemic cells as well as wild-type or multidrug-resistant ABCB5-transfected HEK293 cell lines, but not sensitive or BCRP-transfected multidrug-resistant MDA-MB-231 brea…
Molecular Determinants of Sensitivity or Resistance of Cancer Cells Toward Sanguinarine.
2018
For decades, natural products represented a significant source of diverse and unique bioactive lead compounds in drug discovery field. In Clinical oncology, complete tumors remission is hampered by the development of drug-resistance. Therefore, development of cytotoxic agents that may overcome drug resistance is urgently needed. Here, the natural benzophenanthridine alkaloid sanguinarine has been studied for its cytotoxic activity against multidrug resistance (MDR) cancer cells. We investigated the role of the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5 in drug resistance. Further drug resistance mechanisms analyzed in this study wer…
Simultaneous Determination of Caffeine and Chlorogenic Acids in Green Coffee by UV/Vis Spectroscopy
2017
A simple method for the simultaneous determination of caffeine and chlorogenic acids content in green coffee was reported. The method was based on the use of UV/Vis absorption. It is relevant that the quantification of both caffeine and chlorogenic acids was performed without their preliminary chemical separation despite their spectral overlap in the range 250–350 nm. Green coffee was extracted with 70% ethanol aqueous solution; then the solution was analyzed by spectroscopy. Quantitative determination was obtained analytically through deconvolution of the absorption spectrum and by applying the Lambert-Beer law. The bands used for the deconvolution were the absorption bands of both caffein…
Role of AxyZ Transcriptional Regulator in Overproduction of AxyXY-OprZ Multidrug Efflux System in Achromobacter Species Mutants Selected by Tobramycin
2017
ABSTRACT AxyXY-OprZ is an RND-type efflux system that confers innate aminoglycoside resistance to Achromobacter spp. We investigated here a putative TetR family transcriptional regulator encoded by the axyZ gene located upstream of axyXY-oprZ . An in-frame axyZ gene deletion assay led to increased MICs of antibiotic substrates of the efflux system, including aminoglycosides, cefepime, fluoroquinolones, tetracyclines, and erythromycin, indicating that the product of axyZ negatively regulates expression of axyXY-oprZ . Moreover, we identified an amino acid substitution at position 29 of AxyZ (V29G) in a clinical Achromobacter strain that occurred during the course of chronic respiratory tract…
Multifactorial Modes of Action of Arsenic Trioxide in Cancer Cells as Analyzed by Classical and Network Pharmacology
2018
Arsenic trioxide is a traditional remedy in Chinese Medicine since ages. Nowadays, it is clinically used to treat acute promyelocytic leukemia (APL) by targeting PML/RARA. However, the drug’s activity is broader and the mechanisms of action in other tumor types remain unclear. In this study, we investigated molecular modes of action by classical and network pharmacological approaches. CEM/ADR5000 resistance leukemic cells were similar sensitive to As2O3 as their wild-type counterpart CCRF-CEM (resistance ratio: 1.88). Drug-resistant U87.MG ΔEGFR glioblastoma cells harboring mutated epidermal growth factor receptor were even more sensitive (collateral sensitive) than wild-type U87.MG cells (…
Assessment of tumor-infiltrating TCRV γ 9V δ 2 γδ lymphocyte abundance by deconvolution of human cancers microarrays
2017
Most human blood γδ cells are cytolytic TCRVγ9Vδ2+lymphocytes with antitumor activity. They are currently investigated in several clinical trials of cancer immunotherapy but so far, their tumor infiltration has not been systematically explored across human cancers. Novel algorithms allowing the deconvolution of bulk tumor transcriptomes to find the relative proportions of infiltrating leucocytes, such as CIBERSORT, should be appropriate for this aim but in practice they fail to accurately recognize γδ T lymphocytes. Here, by implementing machine learning from microarray data, we first improved the computational identification of blood-derived TCRVγ9Vδ2+γδ lymphocytes and then appl…
Human ectonucleotidase-expressing CD25 high Th17 cells accumulate in breast cancer tumors and exert immunosuppressive functions
2015
IF 7.644; International audience; Th17 cells contribute to the development of some autoimmune and allergic diseases by driving tissue inflammation. However, the function of Th17 cells during cancer progression remains controversial. Here, we show that human memory CD25(high) Th17 cells suppress T cell immunity in breast cancer. Ectonucleotidase-expressing Th17 cells accumulated in breast cancer tumors and suppressed CD4(+) and CD8(+) T cell activation. These cells expressed both Ror gamma t and Foxp3 genes and secreted Th17 related cytokines. We further found that CD39 ectonucleotisase expression on tumor-infiltrating Th17 cells was driven by TGF-beta and IL-6. Finally, immunohistochemical …
New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease
2019
The Global Burden of Disease Study identified cardiovascular risk factors as leading causes of global deaths and life years lost. Endothelial dysfunction represents a pathomechanism that is associated with most of these risk factors and stressors, and represents an early (subclinical) marker/predictor of atherosclerosis. Oxidative stress is a trigger of endothelial dysfunction and it is a hall-mark of cardiovascular diseases and of the risk factors/stressors that are responsible for their initiation. Endothelial function is largely based on endothelial nitric oxide synthase (eNOS) function and activity. Likewise, oxidative stress can lead to the loss of eNOS activity or even “uncoupli…