Antiproliferative effect of a lectin- and anti-Thy-1.2 antibody-targeted
HPMA copolymer-bound doxorubicin on primary and metastatic human
colorectal carcinoma and on human colorectal carcinoma transfected
with the mouse Thy-1.2 gene.
The aim of this study was to compare the potential of two plant lectins
peanut agglutinin (PNA) and wheat germ agglutinin (WGA), monoclonal
antibody (anti-Thy-1.2), its F(ab')(2) fragments, and galactosamine
as targeting moieties bound to the polymer drug carrier to deliver
a xenobiotic, doxorubicin, to selected cancer cell lines. We have
used primary (SW 480, HT 29) and metastatic (SW 620) human colorectal
cancer cell lines and a transfectant, genetically engineered SW 620
cell line with mouse gene Thy-1.2 (SW 620/T) to test the possibility
of marking human cancer with xenogeneic mouse gene and use it for
effective site-specific targeting. The targeting moieties and doxorubicin
were conjugated to a water-soluble copolymer based on N-(2-hydroxypropyl)methacrylamide
(HPMA) acting as a carrier responsible for controlled intracellular
release of the targeted drug. FACS analysis showed a strong binding
of WGA-FITC to all tested cell lines. Binding of PNA-FITC was considerably
weaker. The in vitro antiproliferative effect of lectin-targeted
HPMA carrier-bound doxorubicin evaluated as (3)HTdR incorporation
reflected both the intensity of the binding and the different sensitivity
of the tested cancer cells lines to doxorubicin. The antiproliferative
effect of conjugates targeted with WGA was comparable to that with
the conjugates targeted with the anti-Thy-1.2 monoclonal antibody
or their F(ab')(2) fragments. The magnitude of the cytotoxic effect
of HPMA-doxorubicin targeted with PNA was lower in all tested cell
lines. While the conjugates with WGA were more cytotoxic, the conjugates
with PNA were more specific as their binding is limited to cancer
cells and to the sites of inflammation. Noncytotoxic conjugates with
a very low concentration of doxorubicin and targeted with PNA, anti-Thy-1.2,
or their F(ab')(2) fragments exerted in some lines (SW 480, SW 620)
low mitogenic activity. The Thy-1.2 gene-transfected SW 620 metastatic
colorectal cancer cell line was sensitive to the antiproliferative
effect of Thy-1.2-targeted doxorubicin as was shown for the Thy-1.
2(+) EL4 cell line and for Thy-1.2(+) concanavalin A-stimulated mouse
T lymphocytes. These results represent the first indication of the
suitability of transfection of human cancer cells with selected targeting
genes for site-specific therapy of malignancies.
%0 Journal Article
%1 Rihova2000b
%A Rihova, B.
%A Jelinkova, M.
%A Strohalm, J.
%A St'astny, M.
%A Hovorka, O.
%A Plocova, D.
%A Kovar, M.
%A Draberova, L.
%A Ulbrich, K.
%D 2000
%J Bioconjug Chem
%K & *Methacrylates ; Activation Agglutinin Agglutinins Animals Antibodies, Antigens, Cell Cells, Colorectal Cultured Division/*drug Doxorubicin/analogs Fab Fragments/toxicity Germ Gov't Humans Immunoglobulin Indicators Lymphocyte Mice Monoclonal/*toxicity Neoplasms Non-U.S. Peanut Proteins/immunology Reagents Recombinant Research Support, T-Lymphocytes/drug Thy-1/genetics/*immunology Transfection Tumor Wheat and derivatives/*toxicity effects effects/immunology
%N 5
%P 664-73
%T Antiproliferative effect of a lectin- and anti-Thy-1.2 antibody-targeted
HPMA copolymer-bound doxorubicin on primary and metastatic human
colorectal carcinoma and on human colorectal carcinoma transfected
with the mouse Thy-1.2 gene.
%U http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?cmd=prlinks&dbfrom=pubmed&retmode=ref&id=10995209
%V 11
%X The aim of this study was to compare the potential of two plant lectins
peanut agglutinin (PNA) and wheat germ agglutinin (WGA), monoclonal
antibody (anti-Thy-1.2), its F(ab')(2) fragments, and galactosamine
as targeting moieties bound to the polymer drug carrier to deliver
a xenobiotic, doxorubicin, to selected cancer cell lines. We have
used primary (SW 480, HT 29) and metastatic (SW 620) human colorectal
cancer cell lines and a transfectant, genetically engineered SW 620
cell line with mouse gene Thy-1.2 (SW 620/T) to test the possibility
of marking human cancer with xenogeneic mouse gene and use it for
effective site-specific targeting. The targeting moieties and doxorubicin
were conjugated to a water-soluble copolymer based on N-(2-hydroxypropyl)methacrylamide
(HPMA) acting as a carrier responsible for controlled intracellular
release of the targeted drug. FACS analysis showed a strong binding
of WGA-FITC to all tested cell lines. Binding of PNA-FITC was considerably
weaker. The in vitro antiproliferative effect of lectin-targeted
HPMA carrier-bound doxorubicin evaluated as (3)HTdR incorporation
reflected both the intensity of the binding and the different sensitivity
of the tested cancer cells lines to doxorubicin. The antiproliferative
effect of conjugates targeted with WGA was comparable to that with
the conjugates targeted with the anti-Thy-1.2 monoclonal antibody
or their F(ab')(2) fragments. The magnitude of the cytotoxic effect
of HPMA-doxorubicin targeted with PNA was lower in all tested cell
lines. While the conjugates with WGA were more cytotoxic, the conjugates
with PNA were more specific as their binding is limited to cancer
cells and to the sites of inflammation. Noncytotoxic conjugates with
a very low concentration of doxorubicin and targeted with PNA, anti-Thy-1.2,
or their F(ab')(2) fragments exerted in some lines (SW 480, SW 620)
low mitogenic activity. The Thy-1.2 gene-transfected SW 620 metastatic
colorectal cancer cell line was sensitive to the antiproliferative
effect of Thy-1.2-targeted doxorubicin as was shown for the Thy-1.
2(+) EL4 cell line and for Thy-1.2(+) concanavalin A-stimulated mouse
T lymphocytes. These results represent the first indication of the
suitability of transfection of human cancer cells with selected targeting
genes for site-specific therapy of malignancies.
@article{Rihova2000b,
__markedentry = {[phpts:6]},
abstract = {The aim of this study was to compare the potential of two plant lectins
[peanut agglutinin (PNA) and wheat germ agglutinin (WGA)], monoclonal
antibody (anti-Thy-1.2), its F(ab')(2) fragments, and galactosamine
as targeting moieties bound to the polymer drug carrier to deliver
a xenobiotic, doxorubicin, to selected cancer cell lines. We have
used primary (SW 480, HT 29) and metastatic (SW 620) human colorectal
cancer cell lines and a transfectant, genetically engineered SW 620
cell line with mouse gene Thy-1.2 (SW 620/T) to test the possibility
of marking human cancer with xenogeneic mouse gene and use it for
effective site-specific targeting. The targeting moieties and doxorubicin
were conjugated to a water-soluble copolymer based on N-(2-hydroxypropyl)methacrylamide
(HPMA) acting as a carrier responsible for controlled intracellular
release of the targeted drug. FACS analysis showed a strong binding
of WGA-FITC to all tested cell lines. Binding of PNA-FITC was considerably
weaker. The in vitro antiproliferative effect of lectin-targeted
HPMA carrier-bound doxorubicin evaluated as [(3)H]TdR incorporation
reflected both the intensity of the binding and the different sensitivity
of the tested cancer cells lines to doxorubicin. The antiproliferative
effect of conjugates targeted with WGA was comparable to that with
the conjugates targeted with the anti-Thy-1.2 monoclonal antibody
or their F(ab')(2) fragments. The magnitude of the cytotoxic effect
of HPMA-doxorubicin targeted with PNA was lower in all tested cell
lines. While the conjugates with WGA were more cytotoxic, the conjugates
with PNA were more specific as their binding is limited to cancer
cells and to the sites of inflammation. Noncytotoxic conjugates with
a very low concentration of doxorubicin and targeted with PNA, anti-Thy-1.2,
or their F(ab')(2) fragments exerted in some lines (SW 480, SW 620)
low mitogenic activity. The Thy-1.2 gene-transfected SW 620 metastatic
colorectal cancer cell line was sensitive to the antiproliferative
effect of Thy-1.2-targeted doxorubicin as was shown for the Thy-1.
2(+) EL4 cell line and for Thy-1.2(+) concanavalin A-stimulated mouse
T lymphocytes. These results represent the first indication of the
suitability of transfection of human cancer cells with selected targeting
genes for site-specific therapy of malignancies.},
added-at = {2011-11-04T13:47:04.000+0100},
author = {Rihova, B. and Jelinkova, M. and Strohalm, J. and St'astny, M. and Hovorka, O. and Plocova, D. and Kovar, M. and Draberova, L. and Ulbrich, K.},
authoraddress = {Institute of Microbiology, Academy of Sciences of the Czech Republic,
142 20 Prague 4-Krc, Czech Republic. Rihova@biomed.cas.cz},
biburl = {https://www.bibsonomy.org/bibtex/290f4d0031e708bd3db73056dc067e055/pawelsikorski},
interhash = {fa810806ea5f296148d94a290faf3582},
intrahash = {90f4d0031e708bd3db73056dc067e055},
journal = {Bioconjug Chem},
keywords = {& *Methacrylates ; Activation Agglutinin Agglutinins Animals Antibodies, Antigens, Cell Cells, Colorectal Cultured Division/*drug Doxorubicin/analogs Fab Fragments/toxicity Germ Gov't Humans Immunoglobulin Indicators Lymphocyte Mice Monoclonal/*toxicity Neoplasms Non-U.S. Peanut Proteins/immunology Reagents Recombinant Research Support, T-Lymphocytes/drug Thy-1/genetics/*immunology Transfection Tumor Wheat and derivatives/*toxicity effects effects/immunology},
language = {eng},
medline-aid = {bc9901696 [pii]},
medline-da = {20001121},
medline-dcom = {20001121},
medline-edat = {2000/09/20 11:00},
medline-fau = {Rihova, B ; Jelinkova, M ; Strohalm, J ; St'astny, M ; Hovorka, O
; Plocova, D ; Kovar, M ; Draberova, L ; Ulbrich, K},
medline-is = {1043-1802 (Print)},
medline-jid = {9010319},
medline-jt = {Bioconjugate chemistry.},
medline-lr = {20051117},
medline-mhda = {2001/02/28 10:01},
medline-own = {NLM},
medline-pl = {UNITED STATES},
medline-pmid = {10995209},
medline-pst = {ppublish},
medline-pt = {Journal Article},
medline-pubm = {Print},
medline-rn = {0 (Antibodies, Monoclonal) ; 0 (Antigens, Thy-1) ; 0 (Immunoglobulin
Fab Fragments) ; 0 (Indicators and Reagents) ; 0 (Methacrylates)
; 0 (Peanut Agglutinin) ; 0 (Recombinant Proteins) ; 0 (Wheat Germ
Agglutinins) ; 23214-92-8 (Doxorubicin) ; 27813-02-1 (hydroxypropyl
methacrylate)},
medline-sb = {IM},
medline-so = {Bioconjug Chem. 2000 Sep-Oct;11(5):664-73.},
medline-stat = {MEDLINE},
number = 5,
owner = {phpts},
pages = {664-73},
timestamp = {2011-11-04T13:47:22.000+0100},
title = {Antiproliferative effect of a lectin- and anti-Thy-1.2 antibody-targeted
HPMA copolymer-bound doxorubicin on primary and metastatic human
colorectal carcinoma and on human colorectal carcinoma transfected
with the mouse Thy-1.2 gene.},
url = {http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?cmd=prlinks\&dbfrom=pubmed\&retmode=ref\&id=10995209},
volume = 11,
year = 2000
}