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Titolo:
CELL-SURFACE BINDING AND CELLULAR INTERNALIZATION PROPERTIES OF SURAMIN, A NOVEL ANTINEOPLASTIC AGENT
Autore:
STEIN CA; KHAN TM; KHALED Z; TONKINSON JL;
Indirizzi:
COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,630 W 168 ST NEW YORK NY 10032
Titolo Testata:
Clinical cancer research
fascicolo: 5, volume: 1, anno: 1995,
pagine: 509 - 517
SICI:
1078-0432(1995)1:5<509:CBACIP>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
FIBROBLAST GROWTH-FACTOR; FACTOR RECEPTOR; ENDOTHELIAL-CELLS; PROSTATE-CANCER; RAPID TURNOVER; OLIGODEOXYNUCLEOTIDES; INHIBITION; DRUG; MUCOPOLYSACCHARIDOSIS; GLYCOSAMINOGLYCAN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
C.A. Stein et al., "CELL-SURFACE BINDING AND CELLULAR INTERNALIZATION PROPERTIES OF SURAMIN, A NOVEL ANTINEOPLASTIC AGENT", Clinical cancer research, 1(5), 1995, pp. 509-517

Abstract

Although suramin has shown promise in preliminary clinical trials as an antineoplastic agent, it is unclear if its mode of action is predominately extracellular or intracellular, We have attempted to address this problem by studying the cellular pharmacology of tritiated suramin([H-3]suramin) in the DU145 and LNCaP prostate cancer cell lines, as well as in HL60 cells, an acute promyelocytic leukemia cell line. In the cell lines studied, significant, multisite, trypsin-insensitive, low-affinity cell surface binding by [H-3]suramin was observed (B-max > 10(6), K-d > 1 mu M). The binding of [H-3]suramin to the cell surface was competitive with respect to a phosphorothioate oligodeoxynucleotide homopolymer of cytidine, 28 bases in length, but was not affected byATP. Use of this competitor allowed us to determine that [H-3]suraminbound to the surface of HL60 cells was internalized via the process of adsorptive endocytosis and was maximal at approximately 6 h. In contrast, binding of suramin to the surface of the prostate cells, but notto that of HL60 cells, was completely abrogated by the presence of albumin (DU145 and LNCaP cells), or by warming to 37 degrees C (DU145 cells only). The dynamics of internalization and compartmentalization ofsuramin in DU145 revealed that within a narrow concentration range, internalization was dependent on time of exposure and drug concentration. Analysis of the exocytosis of suramin from DU145 cells revealed that approximately 64% of the drug was effluxed from a shallow compartment (t(1/2) = 3.15 min) and 31% from a deep compartment (t(1/2) = 433 min); both compartments probably represent endosomes. The results suggest that, because of the complexities of suramin's cellular pharmacology, its mechanism of action may vary signficantly according to cell type.

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Documento generato il 30/11/20 alle ore 17:04:55