Document Detail

Cytotoxic activity, accumulation, and intracellular distribution of anthracycline antibiotics and their conjugates with the epidermal growth factor in sensitive and resistant MCF-7 cells.
MedLine Citation:
PMID:  11112847     Owner:  NLM     Status:  MEDLINE    
Cytotoxic activities, accumulation levels and dynamics, and intracellular distribution of the anthracycline antibiotics doxorubicin (DR) and carminomycin (CM) in the free forms or within conjugates with the epidermal growth factor (EGF) were for the first time compared in human breast carcinoma cell lines MCF-7Wt and MCF-7AdrR. The cytotoxic activities of DR and CM conjugates with EGF were higher than the cytotoxic activities of the free antibiotics in both cell lines. The accumulation levels of the free anthracyclines in both cell lines were lower than those of the conjugates and significantly depended on the cell sensitivities to the antibiotics. On receptor-mediated endocytosis of the anthracycline-EGF conjugates, the accumulation levels did not significantly depend on the cell sensitivities to the antibiotics. Both DR and CM, either free or conjugated with EGF, were mainly accumulated in nuclei. The free drugs were accumulated more rapidly, and the accumulation rates of both free and EGF-conjugated CM were higher than those of DR preparations. The intracellular distribution of the free antibiotics significantly depended on the cell sensitivities to the anthracyclines, whereas the cell sensitivities had no effect on the distribution of the conjugates between the nucleus and cytoplasm. The rate of intracellular degradation of DR and CM delivered to target cells within conjugates with EGF was twice lower than that of the free antibiotics. The difference in the accumulation levels and dynamics and in the intracellular distribution of the free and conjugated DR and CM is likely to underlie the higher cytotoxic activities of the anthracycline conjugates with EGF compared to the free drugs.
S V Lutsenko; N B Feldman; S G Gumanov; A V Rodina; S E Severin
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemistry. Biokhimii͡a     Volume:  65     ISSN:  0006-2979     ISO Abbreviation:  Biochemistry Mosc.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2001-02-02     Completed Date:  2001-02-02     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0376536     Medline TA:  Biochemistry (Mosc)     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1299-304     Citation Subset:  IM    
Moscow Research Institute of Medical Ecology, Moscow, 113149, Russia.
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MeSH Terms
Antibiotics, Antineoplastic / metabolism,  pharmacology*
Breast Neoplasms / metabolism,  pathology
Doxorubicin / metabolism,  pharmacokinetics,  pharmacology*
Epidermal Growth Factor / metabolism*
Tumor Cells, Cultured
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 23214-92-8/Doxorubicin; 62229-50-9/Epidermal Growth Factor

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