The same drug but a different mechanism of action: Comparison of free doxorubicin with two different N-(2-hydroxypropyl)methacrylamide copolymer-bound doxorubicin conjugates in EL-4 cancer cell line

Bioconjugate Chemistry

Volumn 18, Issue 3, 2007, Pages 894-902

  Kovář, Lubomír ^a   Strohalm, Jiří ^b   Chytil, Petr ^b   Mrkvan, Tomáš ^a   Kovář, Marek ^a   Hovorka, Ondřej ^a   Ulbrich, Karel ^b   Říhová, Blanka ^a  

^a INSTITUTE OF MATHEMATICS   (Czech Republic)

^b INSTITUTE OF MACROMOLECULAR CHEMISTRY   (Czech Republic)

Author keywords

[No Author keywords available]

Indexed keywords

CELL CULTURE; CELL SIGNALING; DISEASES; GENE EXPRESSION; GENE EXPRESSION REGULATION; PHOSPHORYLATION; TUMORS;

ANTITUMOR DRUGS; BROAD SPECTRUM; CANCER CELL LINES; DIFFERENT MECHANISMS; DOXORUBICIN; DOXORUBICIN CONJUGATES; EXPOSED TO; HPMA COPOLYMERS; MECHANISM OF ACTION; METHACRYLAMIDES;

CELL DEATH;

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; ANTHRA[1,9 CD]PYRAZOL 6(2H) ONE; CASPASE 3; COPOLYMER; DOXORUBICIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE P38; N (2 HYDROXYPROPYL)METHACRYLAMIDE; STRESS ACTIVATED PROTEIN KINASE;

ANIMAL CELL; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CELL CYCLE REGULATION; CELL PROLIFERATION; CELL SURVIVAL; CELL VIABILITY; CHEMICAL BOND; CONJUGATE; CONTROLLED STUDY; DRUG CONJUGATION; DRUG CYTOTOXICITY; DRUG DISTRIBUTION; DRUG EXPOSURE; DRUG MECHANISM; DRUG POTENCY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; GENE EXPRESSION; HYDROLYSIS; IC 50; MOUSE; NONHUMAN; SIGNAL TRANSDUCTION;

EID: 34347341806     PISSN: 10431802     EISSN: None     Source Type: Journal    
DOI: 10.1021/bc060246e     Document Type: Article

References (22)

1. Rihova, B., Bilej, M., Vetvicka, V., Ulbrich, K., Strohalm, J., Kopecek, J., and Duncan, R. (1989) Biocompatibility of N-(2-hydroxypropyl) methacrylamide copolymers containing adriamycin. Immunogenicity, and effect on haematopoietic stem cells in bone marrow in vivo and mouse splenocytes and human peripheral blood lymphocytes in vitro. Biomaterials 10, 335-42.
2. Maeda, H. (2001) The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv. Enzyme Regul. 41, 189-207.
3. Rihova, B. (1995) Antibody-targeted polymer-bound drugs. Folia Microbiol. (Prague, Czech Repub.) 40, 367-84.
4. Minotti, G., Menna, P., Salvatorelli, E., Cairo, G., and Gianni, L. (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 56, 185-229.
5. Kovar, M., Kovar, L., Subr, V., Etrych, T., Ulbrich, K., Mrkvan, T., Loucka, J., and Rihova, B. (2004) HPMA copolymers containing doxorubicin bound by a proteolytically or hydrolytically cleavable bond: comparison of biological properties in vitro. J. Controlled Release 99, 301-14.
6. Etrych, T., Chytil, P., Jelinkova, M., Rihova, B., and Ulbrich, K. (2002) Synthesis of HPMA copolymers containing doxorubicin bound via a hydrazone linkage. Effect of spacer on drug release and in vitro cytotoxicity. Macromol. Biosci. 2, 43-52.
7. Mrkvan, T., Sirova, M., Etrych, T., Chytil, P., Strohalm, J., Plocova, D., Ulbrich, K., and Rihova, B. (2005) Chemotherapy based on HPMA copolymer conjugates with pH-controlled release of doxorubicin triggers anti-tumor immunity. J. Controlled Release 110, 119-129.
8. Kopecek, J., Rejmanova, P., Strohalm, J., Ulbrich, K., Rihova, B., Chytry, V., Duncan, R., and Lloyd, J. B. (1991) Synthetic polymeric drugs. U.S. Patent 5,037,883.
9. Minko, T., Kopeckova, P., and Kopecek, J. (2001) Preliminary evaluation of caspases-dependent apoptosis signaling pathways of free and HPMA copolymer-bound doxorubicin in human ovarian carcinoma cells. J. Controlled Release 71, 227-37.
10. Hovorka, O., St'astny, M., Etrych, T., Subr, V., Strohalm, J., Ulbrich, K., and Rihova, B. (2002) Differences in the intracellular fate of free and polymer-bound doxorubicin. J. Controlled Release 80, 101-17.
11. Hovorka, O., Etrych, T., Šubr, V., Strohalm, J., Ulbrych, K., and Říhová, B. (2005) HPMA based macromolecular therapeutics: internalization, intracellular pathway and cell death depend on the character of covalent bond between the drug and the peptidic spacer and also on spacer composition. J. Drug Targeting 14, 391-403.
12. Demoy, M., Minko, T., Kopeckova, P., and Kopecek, J. (2000) Time- and concentration-dependent apoptosis and necrosis induced by free and HPMA copolymer-bound doxorubicin in human ovarian carcinoma cells. J. Controlled Release 69, 185-196.
13. Vasey, P. A., Kaye, S. B., Morrison, R., Twelves, C., Wilson, P., Duncan, R., Thomson, A. H., Murray, L. S., Hilditch, T. E., Murray, T., Burtles, S., Fraier, D., Frigerio, E., and Cassidy, J. (1999) Phase I clinical and pharmacokinetic study of PK1 [N-(2-hydroxypropyl)-methacrylamide copolymer doxorubicin]: first member of a new class of chemotherapeutic agents-drug-polymer conjugates. Clin. Cancer Res. 5, 83-94.
14. Rihova, B. (2003) Antibody-targeted HPMA copolymer-bound anthracycline antibiotics. Drugs Future 28, 1189-1210.
15. Ulbrich, K., Subr, V., Strohalm, J., Plocova, D., Jelinkova, M., and Rihova, B. (2000) Polymeric drags based on conjugates of synthetic and natural macromolecules. I. Synthesis and physicochemical characterisation. J. Controlled Release 64, 63-79.
16. Etrych, T., Jelinkova, M., Rihova, B., and Ulbrich, K. (2001) New HPMA copolymers containing doxorubicin bound via pH-sensitive linkage: synthesis and preliminary in vitro and in vivo biological properties. J. Controlled Release 73, 89-102.
17. Kyosseva, S. (2004) Mitogen-activated protein kinase signaling. Int. Rev. Neurobiol. 59, 201-20.
18. Wada, T., and Penninger, J. (2004) Mitogen-activated protein kinases in apoptosis regulation. Oncogene 23, 2838-49.
19. Brantley-Finley, C., Lyle, C., Du, L., Goodwin, M., Hall, T., Szwedo, D., Kaushal, G., and Chambers, T. (2003) The JNK, ERK and p53 pathways play distinct roles in apoptosis mediated by the antitumor agents vinblastine, doxorubicin, and etoposide. Biochem. Pharmacol. 66, 459-69.
20. Seib, F. P., Jones, A. T., and Duncan, R. (2006) Establishment of subcellular fractionation techniques to monitor the intracellular fate of polymer therapeutics I. Differential centrifugation fractionation B16F10 cells and use to study the intracellular fate of HPMA copolymer - doxorubicin. J. Drug Targeting 14, 375-90.
21. Nan, A., Ghandehari, H., Hebert, C., Siavash, H., Nikitakis, N., Reynolds, M., and Sauk, J. J. (2005) Water-soluble polymers for targeted drug delivery to human squamous carcinoma of head and neck. J. Drug Targeting 13, 189-97.
22. Omelyanenko, V., Kopeckova, P., Gentry, C., and Kopecek, J. (1998) Targetable HPMA copolymer-adriamycin conjugates. Recognition, internalization, and subcellular fate. J. Controlled Release 53, 25-37.