Object's details: Relationship between therapeutic efficacy of doxorubicin-transferrin conjugate and expression of P-glycoprotein in chronic erythromyeloblastoid leukemia cells sensitive and resistant to doxorubicin

Provider:Repozytorium Uniwersytetu Łódzkiego

Description

Title:
Relationship between therapeutic efficacy of doxorubicin-transferrin conjugate and expression of P-glycoprotein in chronic erythromyeloblastoid leukemia cells sensitive and resistant to doxorubicin
Creator:
Szwed, Marzena;
Kania, Katarzyna D.;
Jozwiak, Zofia
Contributor:
Szwed Marzena, University of Lodz, Department of Thermobiology, Faculty of Biology and Environmental Protection,;
Kania Katarzyna D., Institute for Medical Biology, Laboratory of Transcriptional Regulation.;
Jozwiak Zofia, University of Lodz, Department of Thermobiology, Faculty of Biology and Environmental Protection.;
szwedma@biol.uni.lodz.pl
Description:
Background Conjugation of anti-neoplastic agents with human proteins is a strategy to diminish the toxic side effects of anthracycline antibiotics. We have developed a novel doxorubicin-transferrin (DOX-TRF) conjugate aimed to direct anticancer drugs against therapeutic targets that display altered levels of expression in malignant versus normal cells. Our previous work has shown that the cellular bio-distribution of the conjugate is dependent on a dynamic balance between influx and efflux processes. Here, we set out to investigate whether P-glycoprotein (P-gp) expression may affect DOXTRF conjugate-induced cellular drug accumulation and cytotoxicity. Results All experiments were carried out on human erythromyeloblastoid cells exhibiting P-gp over-expression (K562/DOX) and its drug sensitive parental line (K562). MTT cytotoxicity, flow cytometry, fluorescence microscopy and RT-PCR assessments revealed that the investigated conjugate (DOX-TRF) possesses a greater cytotoxic potential than free DOX. Conclusion Our data suggest that the newly developed DOXTRF conjugate is a less P-gp dependent substrate than free DOX and, consequently, may be used in a clinical setting to increase treatment efficacy in resistant human tumors.;
Grant no. 545/ 756 of the University of Lodz, Poland.
Object availability:
free access
Rights:
Uznanie autorstwa 3.0 Polska;
http://creativecommons.org/licenses/by/3.0/pl
Date:
2015.06.17;
2014.11.20
Type:
Article
Language:
English
Format:
application/pdf
Publisher:
International Society for Cellular Oncology, IOS Press
Relation:
Cell Oncology (Dordrecht);(2014) 37
Subject:
Doxorubicin;
Transferrin;
Drug carriers;
Multidrug resistance;
P-glycoprotein
Identifier:
2211-3436;
http://hdl.handle.net/11089/9915
Data provider:
Repozytorium Uniwersytetu Łódzkiego

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Object's details: Relationship between therapeutic efficacy of doxorubicin-transferrin conjugate and expression of P-glycoprotein in chronic erythromyeloblastoid leukemia cells sensitive and resistant to doxorubicin

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