Temat: multidrug resistance

Skocz do pozycji: 1.

Tytuł:: Multidrug resistance-associated protein - reduction of expression in human leukaemia cells by antisense phosphorothioate olignucleotides.
Autorzy:: Niewiarowski, Wojciech
Gendaszewska, Edyta
Rębowski, Grzegorz
Wójcik, Marzena
>Mikołajczyk, Barbara
Soszyński, Mirosław
Bartosz, Grzegorz
Tematy:: antisense oligonucleotides
MRP
multidrug resistance; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1044273.pdf Link otwiera się w nowym oknie
Opis:: Multidrug resistance-associated protein (MRP1) causes cellular drug resistance in several cancer cell lines. In this paper we show that antisense oligonucleotides decrease MRP1 expression in human leukaemia cells. We investigated biological activity of a series of 12 linear phosphorothioate oligonucleotides, complementary to several regions of MRP1 mRNA. The oligonucleotides were administered to leukaemia HL60/ADR cells overexpressing MRP1 protein. Then, the level of MRP1 mRNA was determined by means of semiquantitative RT-PCR and the protein level by reaction with specific monoclonal antibodies. Some of the investigated antisense oligonucleotides decrease the expression level of the MRP1 protein by 46% and its mRNA level by 76%.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 2.

Tytuł:: Strategies for overcoming ABC-transporters-mediated multidrug resistance (MDR) of tumor cells
Autorzy:: Borowski, Edward
Bontemps-Gracz, Maria
Piwkowska, Agnieszka
Tematy:: antitumor cytostatics
antimetabolites
multidrug resistance
modulators; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1041364.pdf Link otwiera się w nowym oknie
Opis:: The development of multidrug resistance (MDR) of tumors is a major cause of failure in antitumor chemotherapy. This type of crossresistance is due to the expression of ABC transporter glycoproteins actively effluxing the drug from the cells against the concentration gradient at the expense of metabolic energy, thus preventing the accumulation in cells of therapeutic concentration of active agents. In this review strategies for overcoming this adverse phenomenon are discussed. They comprise the control of expression of MDR glycoprotein transporters and control of the functioning of the expressed transporter proteins. The latter approach is discussed in more detail, comprising the following general strategies: (i) development of compounds that are not substrates of efflux pump(s), (ii) use of agents that inactivate (inhibit) MDR proteins, (iii) design of cytostatics characterized by fast cellular uptake, surpassing their mediated efflux, (iv) use of compounds competing with the drug for the MDR protein-mediated efflux. Positive and negative aspects of these strategies are analysed, with special attention put on strategy based on the use of MDR modulators in combination therapy, allowing the restoration of cytotoxic activity of clinical cytostatics towards resistant tumor cells.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 3.

Tytuł:: Expression of proteins associated with therapy resistance in rhabdomyosarcoma and neuroblastoma tumour cells
Autorzy:: Wieczorek, Agnieszka
Zaremba, Marcin
Pituch-Noworolska, Anna
Opis:: The activity of multidrug resistance (MDR) proteins in tumour cells is associated with an increased resistance to therapy and in consequence with a decreased effectiveness of chemotherapy. The majority of MDR molecules belong to a family of ABC (ATP binding cassette) transporters. Neuroblastoma (NBL) and rhabdomyosarcoma (RMS) are common solid tumours of childhood. The response to therapy is better in NBL, worse in RMS, but still unsatisfactory despite surgery and aggressive chemotherapy. The immunohistochemical staining for p-gp (p-glycoprotein), MRP1 (multidrug resistance associated protein 1), BCRP (breast cancer resistance protein) and LRP (lung resistance protein) expression was performed in primary tumour sections of NBL (10 cases) and RMS (10 cases). A different pattern of MDR expression in NBL and RMS were noted. In NBL, MRP1 was expressed in all studied tumours, p-gp, BCRP only in 3 out of 10 tumours, LRP, in 4 cases. The combination of more than one protein was noted in the majority of NBL tumours. In RMS, the expression of 3 or 4 MDR proteins was noted in 9 cases. The high expression of an MDR protein profile in RMS suggests various mechanisms acting simultaneously, which might explain chemotherapy resistance and a low percentage of long-time survival in this tumour.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Skocz do pozycji: 4.

Tytuł:: Inhibitors of N-glycosylation as a potential tool for analysis of the mechanism of action and cellular localisation of glycoprotein P
Autorzy:: Wojtowicz, Karolina
Szaflarski, Witold
Januchowski, Radosław
Zawierucha, Piotr
Nowicki, Michał
Zabel, Maciej
Tematy:: N-glycosylation
glycoprotein P
multidrug resistance
inhibitors; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1039626.pdf Link otwiera się w nowym oknie
Opis:: Multidrug resistance has for many years attracted attention of numerous investigators. Attempts have also been made to increase efficiency of anti-neoplastic therapy. For this reason, most of efforts have been devoted to analysing proteins engaged in the mechanism of multidrug resistance such as the N-glycosylated membrane protein glycoprotein P. Interestingly, glycosylation probably plays a significant role in the intracellular location and activity of modified proteins. Inhibitors of glycosylation have been demonstrated to alter the activity of glycoprotein P in various ways, depending on the cell line examined. These inhibitors markedly reduce multidrug resistance of cancer cells, thus promoting success of anti-neoplastic therapy. Here, we review the basic knowledge on N-glycosylation inhibitors, their effect on glycoprotein P and their therapeutic potential.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 5.

Tytuł:: Transport of glutathione-conjugates in human erythrocytes.
Autorzy:: Sharma, Rajendra
Awasthi, Sanjay
Zimniak, Piotr
Awasthi, Yogesh
Tematy:: glutathione-conjugates
active transporters
erythrocytes
multidrug resistance; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1044319.pdf Link otwiera się w nowym oknie
Opis:: The last step of detoxification of both endogenous and environmental toxicants is typically a conjugation that produces a bulky hydrophilic molecule. The excretion of such conjugates out of cells is of sufficient biological importance to have led to the evolution of ATP-driven export pumps for this purpose. The substrate specificity of such transporters is broad, and in some cases it has been shown to include not only anionic conjugates but also neutral or weakly cationic drugs. In the present article, we review the molecular identity, functional and structural characteristics of these pumps, mainly on the example of human erythrocytes, and discuss their physiological role in detoxification and in the multidrug resistance phenotype of cancer cells.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 6.

Tytuł:: Interaction of phenothiazines, stilbenes and flavonoids with multidrug resistance-associated transporters, P-glycoprotein and MRP1
Autorzy:: Wesołowska, Olga
Tematy:: multidrug resistance-associated protein 1 (MRP1,ABCC1)
P-glycoprotein (ABCB1)
phenothiazines
multidrug resistance reversal
stilbenes
flavonoids; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1039822.pdf Link otwiera się w nowym oknie
Opis:: Multidrug resistance (MDR) of cancer cells poses a serious obstacle to successful chemotherapy. The overexpression of multispecific ATP-binding cassette transporters appears to be the main mechanism of MDR. A search for MDR-reversing agents able to sensitize resistant cells to chemotherapy is ongoing in the hope of their possible clinical use. Studies of MDR modulators, although they have not produced clinically beneficial effects yet, may greatly enrich our knowledge about MDR transporters, their specificity and mechanism of action, especially substrate and/or inhibitor recognition. In the present review, interactions of three groups of modulators: phenothiazines, flavonoids and stilbenes with both P-glycoprotein and MRP1 are discussed. Each group of compounds is likely to interact with the MDR transporters by a different mechanism. Phenothiazines probably interact with drug binding sites, but they also could indirectly affect the transporter's activity by perturbing lipid bilayers. Flavonoids mainly interact with ABC proteins within their nucleotide-binding domains, though the more hydrophobic flavonoids may bind to regions within transmembrane domains. The possible mechanism of MDR reversal by stilbenes may result from their direct interaction with the transporter (possibly within substrate recognition sites) but some indirect effects such as stilbene-induced changes in gene expression pattern and in apoptotic pathways should also be considered. Literature data as well as some of our recent results are discussed. Special emphasis is put on cases when the interactions of a given compound with both P-glycoprotein and MRP1 have been studied simultaneously.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 7.

Tytuł:: The ability to overcome multidrug resistance of tumor cell lines by novel acridine cytostatics with condensed heterocyclic rings.
Autorzy:: Bontemps-Gracz, Maria
Kupiec, Agnieszka
Antonini, Ippolito
Borowski, Edward
Tematy:: acridine cytostatics
cytotoxic activity
multidrug resistance
antitumor compounds; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1043812.pdf Link otwiera się w nowym oknie
Opis:: Two recently synthesized groups of acridine cytostatics containing fused heterocyclic ring(s): pyrazoloacridines (PAC) and pyrazolopyrimidoacridines (PPAC) were tested in regard to their in vitro cytotoxic activity towards a panel of sensitive and resistant human tumor cell lines. The obtained results corroborate our earlier hypothesis on the essential role of heterocyclic ring fused to the acridine moiety in the ability of acridine cytostatics to overcome multidrug resistance of tumor cells. The presence, location and kind of substituents considerably influenced both the cytotoxic activity of the derivatives and their ability to overcome multidrug resistance. The same factors also affected the cytostatics ability to differentiate between tumor cell lines with various types of drug exporting pumps.
Dostawca treści:: Biblioteka Nauki

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Skocz do pozycji: 8.

Tytuł:: Biological activity of hydantoin derivatives on P-Glycoprotein (ABCB1) of mouse lymphoma cells
Autorzy:: Evaristo, Miguel
Serly, Julianna
Handzlik, Jadwiga
Molnár, Joseph
Amaral, Leonard
Viveiros, Miguel
Spengler, Gabriella
Kieć-Kononowicz, Katarzyna
Opis:: Background: Hydantoin derivatives possess a variety of biochemical and pharmacological properties. Although hydantoin compounds are studied extensively, there are not many studies that investigate their anticancer properties. Materials and Methods: Thirty hydantoin compounds were evaluated for their efflux modulating effects in cancer cells using a rhodamine 123 accumulation assay and real-time fluorometry based on the intracellular accumulation of ethidium bromide. Results: The 30 derivatives were screened by real-time fluorometry for rhodamine 123 accumulation. Among the selected derivatives, compounds SZ-7, LL-9, BS-1, MN-3, P3, RW- 15b, AD-26, RW-13, AD-29 and KF-2 significantly increased the retention of rhodamine 123. Compounds AD-26, AD-29, RW-13, KF-2, BS-1, MN-3, RW-15b and JH-63 showed synergistic effect with doxorubicin on mouse lymphoma cells. Furthermore, compound SZ-7 had indifferent effect with doxorubicin. Conclusion: These results indicated the role of chemical modifications within the hydantoin ring for its potential inhibition of the ABCB1 transporter. The most active structures contained aromatic substituents as well as some tertiary amine fragments.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Skocz do pozycji: 9.

Autorzy:: Wilczak, Magdalena
Surman, Magdalena
Przybyło, Małgorzata
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Skocz do pozycji: 10.

Tytuł:: Transport functions and physiological significance of 76 kDa Ral-binding GTPase activating protein (RLIP76).
Autorzy:: Awasthi, Sanjay
Sharma, Rajendra
Yang, Yusong
Singhal, Sharad
Pikula, Slawomir
Bandorowicz-Pikula, Joanna
Singh, Shivendra
Zimniak, Piotr
Awasthi, Yogesh
Tematy:: RLIP76
RalBP1
glutathione conjugate
multidrug resistance
transport; Pokaż więcej
Wydawca:: Polskie Towarzystwo Biochemiczne
Powiązania:: https://bibliotekanauki.pl/articles/1043688.pdf Link otwiera się w nowym oknie
Opis:: We have recently demonstrated that a previously known Ral-binding GTPase activating protein, RLIP76, can also catalyze ATP-dependent transport of various structurally unrelated xeno- and endobiotics irrespective of their net charge (Awasthi et al., 2000, Biochemistry, 39: 9327). RLIP76 is a non-ATP binding cassette (ABC) protein but it has two ATP-binding sites and shows basal ATPase activity which is stimulated in the presence of its transport substrates (allocrites) such as doxorubicin (DOX) and S-(2,4-dinitrophenyl) glutathione (DNP-SG). Proteoliposomes reconstituted with purified RLIP76 catalyze ATP-dependent, saturable transport of DOX, as well as of glutathione-conjugates including leukotrienes (LTC4) and the GSH-conjugate of 4-hydroxynonenal (GS-HNE). In erythrocytes the majority of transport activity for DOX, GS-HNE, and LTC4 is accounted for by RLIP76. Cells exposed to mild oxidative stress show a rapid and transient induction of RLIP76 resulting in an increased efflux of GS-HNE and acquire resistance to oxidative stress mediated toxicity and apoptosis. Cells transfected with RLIP76 acquire resistance to DOX through increased efflux of the drug suggesting its possible role in the mechanisms of drug-resistance. In this article, we discuss the significance of transport functions of RLIP76 highlighting its role in the defense mechanisms against oxidative injury, and modulation of signaling mechanisms.
Dostawca treści:: Biblioteka Nauki

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