PMID- 20556593
OWN - NLM
STAT- MEDLINE
DCOM- 20100708
LR  - 20211020
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 31
IP  - 4
DP  - 2010 Aug
TI  - Doxorubicin attached to HPMA copolymer via amide bond modifies the glycosylation 
      pattern of EL4 cells.
PG  - 233-42
LID - 10.1007/s13277-010-0019-7 [doi]
AB  - To avoid the side effects of the anti-cancer drug doxorubicin (Dox), we 
      conjugated this drug to a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer 
      backbone. Dox was conjugated via an amide bond (Dox-HPMA(AM), PK1) or a hydrazone 
      pH-sensitive bond (Dox-HPMA(HYD)). In contrast to Dox and Dox-HPMA(HYD), 
      Dox-HPMA(AM) accumulates within the cell's intracellular membranes, including 
      those of the Golgi complex and endoplasmic reticulum, both involved in protein 
      glycosylation. Flow cytometry was used to determine lectin binding and cell 
      death, immunoblot to characterize the presence of CD7, CD43, CD44, and CD45, and 
      high-performance anion exchange chromatography with pulsed amperometric detector 
      analysis for characterization of plasma membrane saccharide composition. 
      Incubation of EL4 cells with Dox-HPMA(AM) conjugate, in contrast to Dox or 
      Dox-HPMA(HYD), increased the amounts of membrane surface-associated 
      glycoproteins, as well as saccharide moieties recognized by peanut agglutinin, 
      Erythrina cristagalli, or galectin-1 lectins. Only Dox-HPMA(AM) increased 
      expression of the highly glycosylated membrane glycoprotein CD43, while 
      expression of others (CD7, CD44, and CD45) was unaffected. The binding sites for 
      galectin-1 are present on CD43 molecule. Furthermore, we present that EL4 treated 
      with Dox-HPMA(AM) possesses increased sensitivity to galectin-1-induced 
      apoptosis. In this study, we demonstrate that Dox-HPMA(AM) treatment changes 
      glycosylation of the EL4 T cell lymphoma surface and sensitizes the cells to 
      galectin-1-induced apoptosis.
FAU - Kovar, Lubomir
AU  - Kovar L
AD  - Department of Immunology and Gnotobiology, Institute of Microbiology, ASCR v.v.i, 
      Videnska 1083, 142 20 Prague 4, Czech Republic. lkovar@biomed.cas.cz
FAU - Etrych, Tomas
AU  - Etrych T
FAU - Kabesova, Martina
AU  - Kabesova M
FAU - Subr, Vladimir
AU  - Subr V
FAU - Vetvicka, David
AU  - Vetvicka D
FAU - Hovorka, Ondrej
AU  - Hovorka O
FAU - Strohalm, Jiri
AU  - Strohalm J
FAU - Sklenar, Jan
AU  - Sklenar J
FAU - Chytil, Petr
AU  - Chytil P
FAU - Ulbrich, Karel
AU  - Ulbrich K
FAU - Rihova, Blanka
AU  - Rihova B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100224
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental 
      Biology and Medicine
JID - 8409922
RN  - 0 (Amides)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Drug Carriers)
RN  - 0 (Galectin 1)
RN  - 0 (Leukosialin)
RN  - 0 (Polymethacrylic Acids)
RN  - 0 (doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Amides/chemistry
MH  - Animals
MH  - Antibiotics, Antineoplastic/*pharmacology
MH  - Apoptosis
MH  - Blotting, Western
MH  - Cell Line, Tumor/drug effects
MH  - Cell Proliferation
MH  - Doxorubicin/*analogs & derivatives/pharmacology
MH  - Drug Carriers
MH  - Endoplasmic Reticulum/metabolism
MH  - Flow Cytometry
MH  - Galectin 1/metabolism
MH  - Glycosylation
MH  - Golgi Apparatus/metabolism
MH  - Leukosialin/metabolism
MH  - Lymphoma, T-Cell/*drug therapy/metabolism/pathology
MH  - Mice
MH  - Polymethacrylic Acids/*pharmacology
EDAT- 2010/06/18 06:00
MHDA- 2010/07/09 06:00
CRDT- 2010/06/18 06:00
PHST- 2009/06/08 00:00 [received]
PHST- 2010/01/16 00:00 [accepted]
PHST- 2010/06/18 06:00 [entrez]
PHST- 2010/06/18 06:00 [pubmed]
PHST- 2010/07/09 06:00 [medline]
AID - 10.1007/s13277-010-0019-7 [doi]
PST - ppublish
SO  - Tumour Biol. 2010 Aug;31(4):233-42. doi: 10.1007/s13277-010-0019-7. Epub 2010 Feb 
      24.