Marine actinomycete crude extracts with potent TRAIL-resistance overcoming activity against breast cancer cells.
Fiche publication
Date publication
avril 2017
Journal
Oncology reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MICHEAU Olivier
Tous les auteurs :
Elmallah MIY, Micheau O, Eid MAG, Hebishy AMS, Abdelfattah MS
Lien Pubmed
Résumé
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent, as it can kill tumor cells selectively. In our search of bioactive natural products to overcome TRAIL-resistance, we isolated 47 actinomycete strains from different sediments and seawater samples collected from the Red Sea coast in Egypt and found four crude extracts (EGY1, EGY3, EGY24 and EGY34) displaying TRAIL sensitizing activity in the resistant breast cancer cell line MDA-MB-231. None of these crude extracts exhibited cytotoxic effect on normal mouse embryonic fibroblasts (MEF), with the exception of EGY34. Analysis of the signaling pathways underlying the sensitization of MDA-MB-231 cells to TRAIL-induced apoptosis, by western blotting, revealed that all crude extracts facilitated initiator caspase‑8/-10 activation upon TRAIL stimulation, but that in addition, EGY3 and EGY34, alone, induced strong ER-stress activation, with the appearance of BiP in the cytosolic extracts. Our results pave the way to the discovery and the development of marine-derived drugs for cancer therapy.
Mots clés
Actinobacteria, chemistry, Animals, Apoptosis, drug effects, Aquatic Organisms, chemistry, Breast Neoplasms, Cell Line, Tumor, Cell Proliferation, drug effects, Cell Survival, drug effects, Complex Mixtures, administration & dosage, Drug Resistance, Neoplasm, drug effects, Female, Fibroblasts, Humans, Mice, Signal Transduction, drug effects, TNF-Related Apoptosis-Inducing Ligand, antagonists & inhibitors
Référence
Oncol. Rep.. 2017 Apr;: