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 been evaluated for their ability to exert cytotoxicity and to bind to nuclear-associated proteins in T-lymphoblast CCRF-CEM cells. Only the oligomers that did not form G-based structures or had a poor structure, under physiological conditions, were able to exert significant cellular growth inhibition effect. The cytotoxicity of these oligomers was related to their binding to the nuclear-associated eEF1A protein, but not to the recognition of nucleolin or other proteins. In particular, GT oligomers adopting a conformation compatible with G-quadruplex, did not exert cytotoxicity and did not bind to eEF1A. The overall results suggest that the ability of oligomers to adopt a G-quadruplex-type secondary structure in a physiological buffer containing 150 mM NaCl is not a prerequisite for antiproliferative effect in haematopoietic cancer cells. The cytotoxicity of G-rich GT oligomers was shown to be tightly related to their binding affinity for eEF1A protein.
Scaggiante
Bruna
B
Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, Italy. scaggiante@bbcm.units.it
Dapas
Barbara
B
Grassi
Gabriele
G
Manzini
Giorgio
G
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C094814:EEF1A1 protein, human; D009841:Oligonucleotides; D015513:Oncogene Proteins; D020648:Peptide Elongation Factor 1