Comparative in vitro and in vivo cytotoxic activity of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and its arabinosyl derivative, (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU), against tumor cells expressing either the Varicella zoster or the Herpes simplex virus thymidine kinase.

Détails

Ressource 1Demande d'une copie Sous embargo indéterminé.
Accès restreint UNIL
Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_1DA3471892FD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Comparative in vitro and in vivo cytotoxic activity of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and its arabinosyl derivative, (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU), against tumor cells expressing either the Varicella zoster or the Herpes simplex virus thymidine kinase.
Périodique
Cancer Gene Therapy
Auteur⸱e⸱s
Grignet-Debrus C., Cool V., Baudson N., Degrève B., Balzarini J., De Leval L., Debrus S., Velu T., Calberg-Bacq C.M.
ISSN
0929-1903 (Print)
ISSN-L
0929-1903
Statut éditorial
Publié
Date de publication
2000
Peer-reviewed
Oui
Volume
7
Numéro
2
Pages
215-223
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Résumé
The inhibitory effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and its arabinosyl derivative (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU) on the growth of both MDA-MB-435 human breast carcinoma and 9L rat gliosarcoma cells expressing the thymidine kinase (tk)-encoding gene of the Varicella zoster virus (VZV) or the Herpes simplex virus (HSV) were evaluated. In vitro, BVDU and BVaraU effectively killed both cell types expressing VZVtk, with 50% inhibitory concentration values ranging from 0.06 to 0.4 microM, whereas ganciclovir (GCV) lacked activity. On HSVtk+ cells, BVDU had high cytotoxic activity, with 50% inhibitory concentration values that were similar to those of GCV, whereas BVaraU was inactive. In vivo, BVDU applied intraperitoneally caused a 50% tumor growth inhibition in nude mice inoculated subcutaneously with VZVtk+ as well as HSVtk+ mammary tumor cells. In mice and at variance with the in vitro results, BVaraU had very little activity against the VZVtk+ mammary cells; GCV had the highest activity on the HSVtk+ cells, resulting in a 50% eradication of the tumors. With the 9L rat gliosarcoma model, the VZVtk/BVDU system completely failed to inhibit the development of VZVtk+ glioma tumors induced subcutaneously in syngeneic rats, although BVDU had a similar 45-minute half-life in both rats and mice. Factors other than degradation of the prodrug and related to the mode of action of these analogs are possibly involved in the observed discrepancies between the in vitro and in vivo results.
Mots-clé
Animals, Antineoplastic Agents/metabolism, Antineoplastic Agents/toxicity, Antiviral Agents/metabolism, Antiviral Agents/toxicity, Arabinofuranosyluracil/analogs & derivatives, Arabinofuranosyluracil/toxicity, Breast Neoplasms/drug therapy, Breast Neoplasms/pathology, Bromodeoxyuridine/analogs & derivatives, Bromodeoxyuridine/metabolism, Female, Genetic Vectors, Herpesvirus 3, Human/drug effects, Herpesvirus 3, Human/enzymology, Humans, Male, Mice, Mice, Nude, Rats, Rats, Inbred F344, Simplexvirus/drug effects, Simplexvirus/enzymology, Thymidine Kinase/biosynthesis, Thymidine Kinase/genetics, Tumor Cells, Cultured
Pubmed
Open Access
Oui
Création de la notice
15/01/2015 15:49
Dernière modification de la notice
20/08/2019 12:53
Données d'usage