Evaluation of the potential of a new ribavirin analog impairing the dissemination of ovarian cancer cells


Autoři: Anaïs Wambecke aff001;  Carine Laurent-Issartel aff001;  Johanne Leroy-Dudal aff001;  Florence Giffard aff002;  Fanny Cosson aff003;  Nadège Lubin-Germain aff003;  Jacques Uziel aff003;  Sabrina Kellouche aff001;  Franck Carreiras aff001
Působiště autorů: Equipe de Recherche sur les Relations Matrice Extracellulaire-Cellules, ERRMECe (EA1391), Institut des Matériaux, I-MAT (FD4122), University of Cergy-Pontoise, MIR, rue Descartes, France aff001;  Normandie University, UNICAEN, INSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment, BioTICLA Axis (Biology and Innovative Therapeutics for Ovarian Cancers), Esplanade de la Paix, Caen, France aff002;  Laboratoire de Chimie Biologique, University of Cergy-Pontoise, mail Gay-Lussac, Cergy-pontoise, France aff003
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225860

Souhrn

Epithelial ovarian cancers are insidious pathologies that give a poor prognosis due to their late discovery and the increasing emergence of chemoresistance. Development of small pharmacological anticancer molecules remains a major challenge. Ribavirin, usually used in the treatment of hepatitis C virus infections and more recently few cancers, has been a suggestion. However, Ribavirin has many side-effects, suggesting that the synthesis of analogs might be more appropriate.

We have investigated the effect of a Ribavirin analog, SRO-91, on cancer cell behavioral characteristics considered as some of the hallmarks of cancer. Two human ovarian adenocarcinoma cell lines (SKOV3 and IGROV1) and normal cells (mesothelial and fibroblasts) have been used to compare the effects of SRO-91 with those of Ribavirin on cell behavior underlying tumor cell dissemination. SRO-91, like Ribavirin, inhibits proliferation, migration, clonogenicity and spheroids formation of cancer cells. Unlike Ribavirin, SRO-91 is preferentially toxic to cancer compared with normal cells. An in vitro physiologically relevant model showed that SRO-91, like Ribavirin or cisplatin, inhibits cancer cell implantation onto peritoneal mesothelium. In conclusion, SRO-91 analog effects on tumor dissemination and its safety regarding non-cancerous (normal) cells are encouraging findings a promising drug for the treatment of ovarian cancer.

Klíčová slova:

Actins – Apoptosis – Cancer cell migration – Cancer treatment – Cell cycle and cell division – Cell staining – DAPI staining – Ovarian cancer


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