ArticleThe Journal of pharmacology and experimental therapeutics2008
A novel human multidrug resistance gene MDR1 variant G571A (G191R) modulates cancer drug resistance and efflux transport.
Article in The Journal of pharmacology and experimental therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 31 citations in OpenAlex.
- Delivery of Oligonucleotides: Efficiency with Lipid Conjugation and Clinical Outcome.Pharmaceutics · 2022Review
- Bypassing P-glycoprotein mediated efflux of afatinib by cyclodextrin complexation - Evaluation of intestinal absorption and anti-cancer activity.Journal of molecular liquids · 2021Article
- Key genes and drug delivery systems to improve the efficiency of chemotherapy.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Inward- and outward-facing X-ray crystal structures of homodimeric P-glycoprotein CmABCB1.Nature communications · 2019Article
- Decreased Disposition of Anticancer Drugs Predominantly Eliminated via the Liver in Patients with Renal Failure.Current drug metabolism · 2019Review
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- The effect of camphor and borneol on rat thymocyte viability and oxidative stress.Molecules (Basel, Switzerland) · 2012Article
- 5k, a novel β-O-demethyl-epipodophyllotoxin analogue, inhibits the proliferation of cancer cells in vitro and in vivo via the induction of G2 arrest and apoptosis.Investigational new drugs · 2011Article
- Do pharmacokinetic polymorphisms explain treatment failure in high-risk patients with neuroblastoma?European journal of clinical pharmacology · 2011Review
- A novel MDR1 GT1292-3TG (Cys431Leu) genetic variation and its effect on P-glycoprotein biologic functions.The AAPS journal · 2010Article
- Comparative description of haplotype structure and genetic diversity of MDR1 (ABCB1) in HIV-positive and HIV-negative populations.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2010Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
The human multidrug resistance gene MDR1 encodes a membrane-bound transporter P-glycoprotein (Pgp) that confers the drug resistance of cancer cells by mediating an ATP-dependent drug efflux transport. We and others have reported a number of functionally significant MDR1 variants, including G1199A and G1199T, that modulate cancer drug resistance and intracellular levels of antivirals. In this report, we describe a novel G571A variant of MDR1 detected in 6.4% of leukemia patients. Because this nucleotide modification gives rise to an amino acid change from Gly to Arg at the 191 amino acid position of Pgp, we have developed and characterized the functional affect of the G571A variant in stable, recombinant cells. Using six chemotherapeutic drugs, doxorubicin HCl, daunorubicin HCl, vinblastine sulfate, vincristine sulfate, taxanes (paclitaxel), and epipodophyllotoxin (etoposide, VP-16), we found that the MDR1(571A) variant selectively reduced the degree of Pgp-mediated resistance in drug-dependent manner. Although there was a minimal effect on doxorubicin and daunorubicin, the MDR1-dependent resistance on vinblastine, vincristine, paclitaxel, and etoposide was reduced by approximately 5-fold. The increased drug sensitivity in MDR1(571A), compared with MDR1(wt), paralleled the intracellular drug levels. These data suggest that individuals with this novel MDR1 variant, the 571A genotype, may be more sensitive to the specific anticancer drugs that are Pgp substrates.
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