Intracellular P-gp contributes to functional drug efflux and resistance in acute myeloid leukaemia

Ferrão, Paulo; Sincock, Paul M.; Cole, Stephen R.; Ashman, Leonie K.

doi:10.1016/s0145-2126(00)00156-9

Cited by 52 publications

(41 citation statements)

References 45 publications

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“…The P-gp localizing on cell membrane plays a role of drug efflux pump, which directly contributes to export of chemotherapeutic drugs from cancerous cells, which is responsible for MDR phenotype of cancerous cells, in spite of the chemotherapeutic drugs are a wide variety of structurally and functionally unrelated with cytotoxicity [28]. 0.013 μm of LMB decreased P-gp on membrane and increased P-gp in cytoplasm of CCRF-CEM/Taxol cells in a time-dependent manner ( Figure 5(b)).…”

Section: Discussionmentioning

confidence: 99%

Cancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cellsCancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cells

Zhu¹,

Zhang²,

Guan³

2012

Health

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Section: Discussionmentioning

confidence: 99%

Cancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cellsCancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cells

Zhu¹,

Zhang²,

Guan³

2012

Health

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“…58,70 Indeed, studies using leukemic cell lines and AML patient samples have shown that the levels of total P-gp (protein or mRNA) correlated better with drug efflux than those of surface P-gp protein. 69 Furthermore, a strong association between intracellular P-gp and intrinsic resistance was observed in a human colon carcinoma clone, which did not express P-gp on the plasma membrane. 70 Nevertheless, other studies claim that intracellular P-gp does not seem to have a (major) role in drug resistance.…”

Section: P-gp Synthesis Cellular Localization Expression and Functionmentioning

confidence: 98%

“…57,64,68 P-gp may also be present in intracellular vesicles actively contributing to drug sequestration and removal from cells. 66,69 Several studies have suggested that intracellular P-gp also contributes to drug resistance. 58,70 Indeed, studies using leukemic cell lines and AML patient samples have shown that the levels of total P-gp (protein or mRNA) correlated better with drug efflux than those of surface P-gp protein.…”

Section: P-gp Synthesis Cellular Localization Expression and Functionmentioning

confidence: 99%

The network of P-glycoprotein and microRNAs interactions

et al. 2013

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Overexpression of P‐glycoprotein (P‐gp) contributes to the multidrug resistance (MDR) phenotype found in many cancer cells. P‐gp has been identified as a promising molecular target, although attempts to find successful therapies to counteract its function as a drug efflux pump have largely failed to date. Apart from its role in drug efflux, P‐gp may have other cellular functions such as being involved in apoptosis, and is found in various locations in the cell. Its expression is highly regulated, namely by microRNAs (miRNAs or miRs). In addition, P‐gp may regulate the expression of miRs in the cell. Furthermore, both P‐gp and miRs may be found in microvesicles or exosomes and may be transported to neighboring, drug‐sensitive cells. Here, we review this current issue together with recent evidence of this network of interactions between P‐gp and miRs.

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“…Many different mechanisms have been suggested to explain the development of MDR phenotype in cancer cells, such as a change in the specific target of a drug (1), the reduced uptake or increased efflux of a drug (3,4), a differential compartmentalization (5,6), an increased rate of detoxification of a drug (4,7), an increased ability to repair DNA damage (4,8), gene amplification (9,10), and an increase in the activity of survival proteins and reduced capacity to enter apoptosis (11,12). In some cases of MDR, one or more of these mechanisms may act at a time.…”

mentioning

confidence: 99%

Overcoming Drug-Resistant Cancer by a Newly Developed Copper Chelate through Host-Protective Cytokine-Mediated Apoptosis

Mookerjee

Basu

Dutta

et al. 2006

Clinical Cancer Research

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Purpose: Previously, we have synthesized and characterized a novel Cu(II) complex, copper N-(2-hydroxy acetophenone) glycinate (CuNG). Herein, we have determined the efficacy of CuNG in overcoming multidrug-resistant cancer using drug-resistant murine and human cancer cell lines. Experimental Design: Action of CuNG following single i.m. administration (5 mg/kg body weight) was tested in vivo on doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox)b earing mice and doxorubicin-resistant sarcoma 180^bearing mice. Tumor size, ascitic load, and survival rates were monitored at regular intervals. Apoptosis of cancer cells was determined by cell cycle analysis, confocal microscopy, Annexin V binding, and terminal deoxynucleotidyl transferase^mediated dUTP nick end labeling assay ex vivo. IFN-g and tumor necrosis factor-a were assayed in the culture supernatants of in vivo and in vitro CuNG-treated splenic mononuclear cells from EAC/Dox-bearing mice and their apoptogenic effect was determined. Source of IFN-g and changes in number of T regulatory marker-bearing cells in the tumor site following CuNG treatment were investigated by flow cytometry. Supernatants of in vitro CuNG-treated cultures of peripheral blood mononuclear cells from different drug-insensitive cancer patients were tested for presence of the apoptogenic cytokine IFN-g and its involvement in induction of apoptosis of doxorubicin-resistant CEM/ADR5000 cells. Results: CuNG treatment could resolve drug-resistant cancers through induction of apoptogenic cytokines, such as IFN-g and/or tumor necrosis factor-a, from splenic mononuclear cells or patient peripheral blood mononuclear cells and reduce the number of Tregulatory marker-bearing cells while increase infiltration of IFN-g-producingTcells in the ascetic tumor site. Conclusion: Our results show the potential usefulness of CuNG in immunotherapy of drugresistant cancers irrespective of multidrug resistance phenotype.

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Intracellular P-gp contributes to functional drug efflux and resistance in acute myeloid leukaemia

Cited by 52 publications

References 45 publications

Cancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cellsCancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cells

Cancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cellsCancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cells

The network of P-glycoprotein and microRNAs interactions

Overcoming Drug-Resistant Cancer by a Newly Developed Copper Chelate through Host-Protective Cytokine-Mediated Apoptosis

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