Search results for "P-Glycoprotein"

Synthesis, computational docking and biological evaluation of celastrol derivatives as dual inhibitors of SERCA and P-glycoprotein in cancer therapy.

2021

Abstract A series of eleven celastrol derivatives was designed, synthesized, and evaluated for their in vitro cytotoxic activities against six human cancer cell lines (A549, HepG2, HepAD38, PC3, DLD-1 Bax-Bak WT and DKO) and three human normal cells (LO2, BEAS-2B, CCD19Lu). To our knowledge, six derivatives were the first example of dipeptide celastrol derivatives. Among them, compound 3 was the most promising derivative, as it exhibited a remarkable anti-proliferative activity and improved selectivity in liver cancer HepAD38 versus human normal hepatocytes, LO2. Compound 6 showed higher selectivity in liver cancer cells against human normal lung fibroblasts, CCD19Lu cell line. The Ca2+ mob…

The antitumor activities of curcumin and its isoxazole analogue are not affected by multiple gene expression changes in an MDR model of the MCF-7 bre…

2007

We examined the effects of curcumin and of its isoxazole analogue MR 39 in the MCF-7 breast cancer cell line and in its multidrug-resistant (MDR) variant MCF-7R. In comparison with MCF-7, MCF-7R lacks estrogen receptor alpha (ERalpha) and overexpressess P-glycoprotein (P-gp), different IAPs (inhibitory of apoptosis proteins) and COX-2. Through analyses of the effects on cell proliferation, cycling and death, we have observed that the antitumor activity of curcumin and of the more potent (approximately two-fold) MR 39 is at least equal in the MDR cell line compared to the parental MCF-7. Similar results were observed also in an MDR variant of HL-60 leukemia. RT-PCR evaluations performed in M…

THE EFFECT OF CYP3A5 AND ABCB1 SINGLE NUCLEOTIDE POLYMORPHISMS ON TACROLIMUS DOSE REQUIREMENTS IN CAUCASIAN LIVER TRANSPLANT PATIENTS

2008

Cytotoxicity and inhibition of P-glycoprotein by selected medicinal plants from Thailand.

2014

Abstract Ethnopharmacological relevance Thai medicine has a long tradition of tonifying medicinal plants. In the present investigation, we studied the flower extracts of Jasminum sambac, Mammea siamensis, Mesua ferrea, Michelia alba, Mimusops elengi, and Nelumbo nucifera and speculated that these plants might influence metabolism and substance flow in the body. Materials and methods Isolation of porcine brain capillary endothelial cells (PBCECs) as well as multidrug-resistance CEM/ADR5000 leukemia cells, MDA-M;B-231 breast cancer, U-251 brain tumor, and HCT-116 colon cancer cells were used. The calcein-acetoxymethylester (AM) assay was used to measure inhibition of P-glycoprotein transport.…

Activity of Drug Efflux Transporters in Tumor Cells Under Hypoxic Conditions

2008

Tumor cells exhibit mechanisms by which chemotherapeutic drugs can be actively pumped out of the cell (e.g., p-glycoprotein pGP, MRP1), resulting in a multidrug resistant phenotype. Many human tumors show pronounced hypoxia which can result in a local ATP depletion which in turn may compromise the efficacy of these transporters. The aim of this study was therefore to assess the transport activity and expression of drug transporters under hypoxic conditions. Prostate carcinoma cells (R3327-AT1) were exposed to hypoxia (pO2≶0.5 mmHg) for up to 24h and pump activity was determined by an efflux assay. The results showed that exposing cells to hypoxia for 3–6 h led to a moderate increase in pGP …

Kinetic Characterization of Secretory Transport of a New Ciprofloxacin Derivative (CNV97100) across Caco-2 Cell Monolayers**This work has been submit…

2002

The kinetics of transport of a new fluoroquinolone antibiotic (CNV97100) and its analogs were characterized using the Caco-2 cell culture model. Unidirectional permeabilities of these analogs were greater (p < 0.05) than that of ciprofloxacin. The absorptive permeabilities (P(AB)) of 4'-N-substituted analogs (CNV97101-104) were 400-600% greater, whereas the secretory permeability (P(BA)) was 25-80% greater than unsubstituted analogs because CNV97101-104 were poor substrates for efflux transporters (efflux ratio approximately 1). The transport of compounds without 4'-N-substitution (i.e., ciprofloxacin and CNV97100) favored secretion (efflux ratio approximately 4). Further characterization o…

Overcoming of P-glycoprotein-mediated multidrug resistance of tumors in vivo by drug combinations

2014

Summary Inhibition of P-glycoprotein represents an attractive possibility to modulate resistance of cancer cells to anticancer drugs. One major strategy to overcome P-glycoprotein-mediated multidrug resistance (MDR) of tumors is to increase intracellular concentrations of anticancer drugs. This can be achieved by blocking of P-glycoprotein-mediated drug efflux using synthetic or natural small molecules or monoclonal antibodies, which bind to various parts of the efflux channel. Another possibility to increase intracellular drug concentrations can be reached by nanoparticles. A further major strategy to overcome MDR involves the downregulation of P-glycoprotein expression either by therapeut…

Intertissue Flow of Glutathione (GSH) as a Tumor Growth-promoting Mechanism

2011

B16 melanoma F10 (B16-F10) cells with high glutathione (GSH) content show high metastatic activity in vivo. An intertissue flow of GSH, where the liver is the main reservoir, can increase GSH content in metastatic cells and promote their growth. We have studied here possible tumor-derived molecular signals that could activate GSH release from hepatocytes. GSH efflux increases in hepatocytes isolated from mice bearing liver or lung metastases, thus suggesting a systemic mechanism. Fractionation of serum-free conditioned medium from cultured B16-F10 cells and monoclonal antibody-induced neutralization techniques facilitated identification of interleukin (IL)-6 as a tumor-derived molecule prom…

Role of P-Glycoprotein for Resistance of Tumors to Anticancer Drugs: From Bench to Bedside

2014

Success of cancer chemotherapy is limited by simultaneous resistance towards many anticancer drugs making clinical combination therapy protocols less efficient. P-glycoprotein represents an efflux pump of the ABC transporter family, which recognizes and extrudes anticancer drugs of diverse chemical classes and biochemical functions. The P-glycoprotein-mediated profile of cross-resistance has been termed multidrug resistance (MDR). In our investigations, we focused on MDR of in vivo tumor lines maintained in mice. The development of in vivo resistance towards anthracyclines (doxorubicin, daunorubicin) in L1210 and S180 ascites tumor lines was accompanied with decreased uptake and increased e…

Novel Stilbene-Based Antileukemic Agents Active in P-Glycoprotein Expressing and Apoptosis-Resistant Acute Leukaemia Cell Lines.

2005

Abstract The stilbene scaffold is a basic element for a number of biologically active natural and synthetic compounds and in accordance with Evans’ definition it can be considered as a privileged structure. One of the most relevant and studied stilbenes is Resveratrol, a phytoalexin present in grapes, endowed with chemopreventive and chemotherapeutic properties and able to induce apoptosis in different cancer cell lines. Since reduced apoptosis has been implicated in the development and progression of malignant tumors and in the occurrence of chemoresistant phenotypes, resveratrol-induced apoptosis might therefore contribute to its antitumor activity. However, resveratrol is a not potent cy…