A silent polymorphism in the MDR1 gene changes substrate specificity.
AuthorsKimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM,
JournalScience
PubMed ID17185560
'Synonymous single-nucleotide polymorphisms (SNPs) do not produce altered coding sequences, and therefore they are not expected to change the function of the protein in which they occur. We report that a synonymous SNP in the Multidrug Resistance 1 (MDR1) gene, part of a haplotype previously linked to altered function of ... More
Multidrug resistance gene G1199A polymorphism alters efflux transport activity of P-glycoprotein.
AuthorsWoodahl EL, Yang Z, Bui T, Shen DD, Ho RJ
JournalJ Pharmacol Exp Ther
PubMed ID15100388
'The significance of the human multidrug resistance gene (MDR1) G1199A polymorphism, resulting in a Ser400Asn modification in P-glycoprotein (P-gp), remains unclear. We have developed stable recombinant LLC-PK1 epithelial cells expressing either MDR1wt or MDR11199 to evaluate functional consequences of G1199A [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide]. P-gp activity observed in MDR1wt and MDR11199 cells ... More
Evidence for the locations of distinct steroid and Vinca alkaloid interaction domains within the murine mdr1b P-glycoprotein.
AuthorsGruol DJ, King MN, Kuehne ME
JournalMol Pharmacol
PubMed ID12391288
'P-glycoproteins (P-gp) cause the efflux of a wide variety of unrelated hydrophobic compounds out of cells. However, the locations of the sites at which different classes of molecules initially interact with the protein are not well defined. A unique system was developed to search for P-gp drug-interaction domains using mutational ... More
The influence of combretastatin A-4 and vinblastine on interstitial fluid pressure in BT4An rat gliomas.
AuthorsEikesdal HP, Landuyt W, Dahl O
JournalCancer Lett
PubMed ID11867206
'The influence of combretastatin A-4 disodium phosphate (CA-4, 50mg/kg intraperitoneally (i.p.)) and vinblastine (2mg/kg i.p.) on interstitial fluid pressure (IFP) was assessed in BT4An rat gliomas implanted subcutaneously in the neck. Furthermore the growth inhibitory effect of vinblastine and the distribution of fluorescence-conjugated vinblastine (BODIPY-vinblastine) were investigated. Tumors at different ... More
Genistein arrests cell cycle progression of A549 cells at the G(2)/M phase and depolymerizes interphase microtubules through binding to a unique site of tubulin.
Genistein (4',5,7-trihydroxyisoflavone), an isoflavone, is a major constituent of soyfoods. It has potential antiproliferative activity against several tumor types. We have examined the effect of genistein on cellular microtubules as well as its binding with purified tubulin in vitro. Cell viability experiments using human non-small lung epithelium carcinoma cells (A549) ... More
Drug resistance conferred by MDR1 expression in spheroids formed by glioblastoma cell lines.
AuthorsKolchinsky A, Roninson IB
JournalAnticancer Res
PubMed ID9413166
Three-dimensional cell cultures (spheroids) provide an in vitro approximation of solid tumors in vivo. Some mechanisms of drug resistance were reported to differ in their effects on monolayer and spheroid cells. We have compared the effect on the expression of P-glycoprotein (Pgp), the MDR1 gene product, on vinblastine resistance in ... More
Effect of stathmin on the sensitivity to antimicrotubule drugs in human breast cancer.
AuthorsAlli E, Bash-Babula J, Yang JM, Hait WN
JournalCancer Res
PubMed ID12460900
Stathmin is a p53-regulated protein known to influence microtubule dynamics. Because several chemotherapeutic agents used to treat breast cancer alter the dynamic equilibrium of tubulin polymerization, stathmin may play an important role in determining the sensitivity to these drugs. Therefore, we evaluated the effect of stathmin expression on the action ... More
Functional characterization of coding polymorphisms in the human MDR1 gene using a vaccinia virus expression system.
AuthorsKimchi-Sarfaty C, Gribar JJ, Gottesman MM
JournalMol Pharmacol
PubMed ID12065748
The human MDR1-encoded transporter is a 170-kDa plasma membrane glycoprotein [P-glycoprotein (P-gp)] capable of binding and energy-dependent extrusion of structurally diverse organic compounds and drugs. P-gp seems to play a significant role in uptake, distribution, and excretion of many different drugs. To determine whether common polymorphic forms of P-gp are ... More