Meloxicam increases intracellular accumulation of doxorubicin via downregulation of multidrug resistance-associated protein 1 (MRP1) in A549 cells

Chen, S F; Zhang, Z Y; Zhang, J L

doi:10.4238/2015.november.18.18

Cited by 9 publications

(9 citation statements)

References 39 publications

(45 reference statements)

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“…The protein kinase C activator and COX-2 inducer phorbol 12-myristate 13-acetate (PMA; 10 nM; Figure 3) induced MRP1 expression in MRP1-overexpressing A549 cells. 218 This could functionally be confirmed as PMA slightly decreased daunorubicin accumulation in MRP1-overexpressing 2R120 cells, but not in GLC 4 /ADR cells at 20 nM. 131…”

Section: Surface Active Agentsmentioning

confidence: 92%

The A‐B‐C of small‐molecule ABC transport protein modulators: From inhibition to activation—a case study of multidrug resistance‐associated protein 1 (ABCC1)

Wiese

Stefan

2019

Medicinal Research Reviews

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Several mechanisms of pharmacokinetic, metabolic, and regulatory nature have been elucidated to take part or act in concert in the phenomenon of multidrug resistance (MDR). MDR is characterized by cross‐resistance of cells against chemotherapeutic agents, which are used for treatment of e.g., cancer, bacterial infections, or human immunodeficiency virus (HIV) infections. One group of proteins that combines all three stated aspects—the metabolism and distribution of drugs as well as their own regulation—is adenosine triphosphate‐binding cassette (ABC) transporters. These efflux pumps use the energy of adenosine triphosphate hydrolysis for drug translocation from the membrane and the cytosol to the extracellular space, often with cotransport of a cosubstrate. Multidrug resistance‐associated protein 1 (MRP1, ABCC1) had been discovered as one major key player in cancer‐related MDR. The xenobiotic substrates include anthracyclines, vinca alkaloids, podophyllotoxins, as well as glutathione (GSH)‐adducts of certain cytostatics. Contrary to other transport proteins involved in cancer‐related MDR the activity of MRP1 is related to the GSH content of cells. A modern strategy to overcome MRP1‐associated MDR is besides its inhibition the activation of GSH efflux, enforcing cell death due to cellular stress. In addition, it has recently been found that MRP1 contributes to the β‐amyloid protein clearance in Alzheimer's disease (AD). Collectively, transport activation of MRP1 is of therapeutic value, and furthermore helps to elucidate the transport protein function and the mechanisms behind it. This review is meant to summarize the known concepts of MRP1 activation, which might contribute to a further understanding of MRP1 in particular and ABC transporters in general.

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Section: Surface Active Agentsmentioning

confidence: 92%

The A‐B‐C of small‐molecule ABC transport protein modulators: From inhibition to activation—a case study of multidrug resistance‐associated protein 1 (ABCC1)

Wiese

Stefan

2019

Medicinal Research Reviews

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“…The newest report on this has been made by Chen et al. reporting on meloxicam and celecoxib . The in vitro approach in A549 cells showed that 10 μM meloxicam was superior compared to 10 μM celecoxib when it came to potentiate the toxicity of doxorubicin.…”

Section: Pharmacological and Experimental Drugs And Synthetic Analogsmentioning

confidence: 99%

Small‐molecule inhibitors of multidrug resistance‐associated protein 1 and related processes: A historic approach and recent advances

Stefan

Wiese

2018

Medicinal Research Reviews

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Multidrug resistance-associated protein 1 (MRP1, ABCC1) is an ATP-binding cassette (ABC) transport protein. This efflux pump uses the energy of ATP hydrolysis to export structurally diverse antineoplastic agents in human cancers. The upregulation of MRP1 (either inherent or acquired) is one major reason for the occurrence of the phenomenon called multidrug resistance (MDR). MDR is characterized by a reduced outcome of chemotherapy due to the active intracellular clearance of cytostatic drugs below the necessary effect concentration. Much effort has been made to overcome MDR, which implied high-throughput screenings of already known pharmacological and natural compounds, modification of intrinsic substrates, as well as design and synthesis of new inhibitors. This review is meant not only to summarize the most recent results over the past 10 years, but also to highlight major achievements regarding reversal of MRP1-mediated MDR, from the time of its discovery until today. The focus lies on small-molecule compounds that feature either direct MRP1 inhibition/transport blockage, toxicity against MRP1-overexpressing cells, inhibition/modification of intracellular processes necessary for MRP1 function, or modification of MRP1-related metabolic and genomic mechanisms. Considering all aspects, this review might be useful to (re)consider possible strategies to overcome MRP1-mediated MDR. Furthermore, it may be the basis for developing new, even better, highly potent, less toxic, and selective (as well as broad-spectrum) MRP1 inhibitors that will enter clinical evaluations in different malignancies and finally conduce to overcome MDR in general.

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“…The 1 mL DEX-SS-IND/DOX micelle solution was transferred into a dialysis membrane (MWCO 7.0 kDa) and then immersed in 20 mL incubation media with constant shaking at 70 rpm at 37°C. At predetermined time intervals (1,2,4,6,8,10,12,24,36, and 48 hours), the samples were collected and replaced with fresh medium. DOX content was measured using fluorescence spectrophotometry.…”

Section: Synthesis and Characterization Of Dex-ss-indmentioning

confidence: 99%

“…6,7 The antitumor agent doxorubicin (DOX) is widely used for the treatment of various solid tumors via interacting with DNA through intercalation and inhibiting topoisomerase II, but it is also a substrate for MRPs. 8 The abnormal increase of drug efflux and reduced intracellular drug concentration lead to DOX resistance. In addition, it has several therapeutic limitations, including irreversible nephrotoxicity, neurotoxicity, and cardiotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer

Zhou¹,

Wang²,

Ying³

et al. 2017

IJN

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Multidrug resistance (MDR) against chemotherapeutic agents has become one of the major obstacles to successful cancer therapy and MDR-associated proteins (MRPs)-mediated drug efflux is the key factor for MDR. In this study, a redox-responsive polymer based on dextran (DEX) and indomethacin (IND), which could reduce MRPs-mediated efflux of chemotherapeutics, was synthesized, and the obtained polymer could spontaneously form stable micelles with well-defined core-shell structure and a uniform size distribution with an average diameter of 50 nm and effectively encapsulate doxorubicin (DOX); the micelles contain a disulfide bridge (cystamine, SS) between IND and DEX (DEX-SS-IND). In vitro drug release results indicated that DEX-SS-IND/DOX micelles could maintain good stability in a stimulated normal physiological environment and promptly depolymerized and released DOX in a reducing environment. After incubating DEX-SS-IND/DOX micelles with drug-resistant tumor (MCF-7/ADR) cells, the intracellular accumulation and retention of DOX were significantly increased under the synergistic effects of redox-responsive delivery and the inhibitory effect of IND on MRPs. In vitro cytotoxicity showed that DEX-SS-IND/DOX micelles exhibited higher cytotoxicity against MCF-7/ADR cells. Moreover, DEX-SS-IND/DOX micelles showed significantly enhanced inhibition of tumor in BALB/c nude mice bearing MCF-7/ADR tumors and reduced systemic toxicity. Overall, the cumulative evidence indicates that DEX-SS-IND/DOX micelles hold significant promise for overcoming MDR for cancer therapy.

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Meloxicam increases intracellular accumulation of doxorubicin via downregulation of multidrug resistance-associated protein 1 (MRP1) in A549 cells

Cited by 9 publications

References 39 publications

The A‐B‐C of small‐molecule ABC transport protein modulators: From inhibition to activation—a case study of multidrug resistance‐associated protein 1 (ABCC1)

The A‐B‐C of small‐molecule ABC transport protein modulators: From inhibition to activation—a case study of multidrug resistance‐associated protein 1 (ABCC1)

Small‐molecule inhibitors of multidrug resistance‐associated protein 1 and related processes: A historic approach and recent advances

Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer

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