Interaction of G-rich GT oligonucleotides with nuclear-associated eEF1A is correlated with their antiproliferative effect in haematopoietic human cancer cell lines.

G-rich GT oligonucleotides with a different content of G clusters have beenevaluated for their ability to exert cytotoxicity and to bind to nuclear-associatedproteins in T-lymphoblast CCRF-CEM cells. Only the oligomersthat did not form G-based structures or had a poor structure, under physiologicalconditions, were able to exert significant cellular growth inhibitioneffect. The cytotoxicity of these oligomers was related to their bindingto the nuclear-associated eEF1A protein, but not to the recognition ofnucleolin or other proteins. In particular, GT oligomers adopting a conformationcompatible with G-quadruplex, did not exert cytotoxicity and didnot bind to eEF1A. The overall results suggest that the ability of oligomersto adopt a G-quadruplex-type secondary structure in a physiological buffercontaining 150 mm NaCl is not a prerequisite for antiproliferative effect inhaematopoietic cancer cells. The cytotoxicity of G-rich GT oligomers wasshown to be tightly related to their binding affinity for eEF1A protein.