ABCG2/BCRP: Specific and Nonspecific Modulators

Peña-Solórzano, Diana; Stark, Simone; König, Burkhard; Sierra, César A.; Ochoa‐Puentes, Cristian

doi:10.1002/med.21428

Cited by 58 publications

(57 citation statements)

References 198 publications

(266 reference statements)

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“…The main focus of ABC transporter research within the last 40 years laid mostly on the search/finding and improvement/development of inhibitors to treat MDR‐conferring cancer cells . Here again, the first discoveries concerned P‐gp, as this was the very first described ABC transporter involved in the MDR phenotype .…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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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“…Drug resistance is closely related to increased drug efflux mediated by an energy-dependent mechanism involving the ABC (ATP binding cassette) transporters, mainly ABCB1 (ATP binding cassette subfamily B member 1), ABCC1 (ATP binding cassette subfamily C member 1), and ABCG2 (ATP binding cassette subfamily G member)[24]. Moreover, it has been reported that ABCG2 plays an important role in regulating chemo-resistance in gastric cancer[22].…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-145 exerts tumor-suppressive and chemo-resistance lowering effects by targeting CD44 in gastric cancer

Zeng

Wang

et al. 2017

WJG

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AIMTo determine the potential roles of CD4 and microRNA (miR)-145 in gastric cancer.METHODSThe levels of CD44 and miR-145 were determined in gastric cancer cells. Quantitative real-time polymerase chain reaction was used to measure to the level of CD44 mRNA. A luciferase reporter assay and western blotting were performed to examine the effect of miR-145 on CD44 expression. Tumor sphere and MTT assays were carried out to evaluate the self-renewal and chemo-resistance properties of gastric cancer cells.RESULTSThe expression of CD44 was greatly increased and miR-145 was decreased in gastric cancer cells that were highly enriched in cancer stem cells (CSCs). The results demonstrated that miR-145 regulated CD44 by targeting directly the CD44 3’-untranslated region (3’-UTR). In gastric cancer cells, overexpression of miR-145 repressed the activity of the CD44 3’-UTR, and disruption of miR-145/CD44 3’-UTR interactions abrogated the silencing effects. In addition, miR-145 inhibition stimulated CD44 3’-UTR activity and disruption of miR-145/CD44 3’-UTR interactions abrogated this stimulatory effect. Enforced CD44 expression greatly increased tumor sphere formation and chemo-resistance in gastric cancer cells. Furthermore, the inhibition of CSCs and the chemo-sensitivity of gastric cancer cells treated with miR-145 were significantly abrogated by overexpression of CD44.CONCLUSIONmiR-145 targeting of CD44 plays critical roles in the regulation of tumor growth and chemo-resistance in gastric cancer.

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“…Driven by the hypothesis that drug resistance in the treatment of cancers could be influenced by the co‐administration of BCRP‐inhibitors, numerous compounds were tested for their ability to modulate BCRP transport functions (for a recent review, see Peña‐Solórzano, Stark, König, Sierra, & Ochoa‐Puentes, ). The most consistent results were determined with individual flavonoids, including quercetin, silymarin, daidzein and other polyphenols, as well as the natural stilbenoid resveratrol.…”

Section: Transporter Polymorphismsmentioning

confidence: 99%

Population variability in animal health: Influence on dose–exposure–response relationships: Part I: Drug metabolism and transporter systems

Martinez

Court

Fink‐Gremmels

et al. 2018

Vet Pharm & Therapeutics

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There is an increasing effort to understand the many sources of population variability that can influence drug absorption, metabolism, disposition, and clearance in veterinary species. This growing interest reflects the recognition that this diversity can influence dose-exposure-response relationships and can affect the drug residues present in the edible tissues of food-producing animals. To appreciate the pharmacokinetic diversity that may exist across a population of potential drug product recipients, both endogenous and exogenous variables need to be considered. The American Academy of Veterinary Pharmacology and Therapeutics hosted a 1-day session during the 2017 Biennial meeting to explore the sources of population variability recognized to impact veterinary medicine. The following review highlights the information shared during that session. In Part I of this workshop report, we consider sources of population variability associated with drug metabolism and membrane transport. Part II of this report highlights the use of modeling and simulation to support an appreciation of the variability in dose-exposure-response relationships.

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ABCG2/BCRP: Specific and Nonspecific Modulators

Cited by 58 publications

References 198 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)

MicroRNA-145 exerts tumor-suppressive and chemo-resistance lowering effects by targeting CD44 in gastric cancer

Population variability in animal health: Influence on dose–exposure–response relationships: Part I: Drug metabolism and transporter systems

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