Study of the Function of G-Rich Aptamers Selected for Lung Adenocarcinoma.

Abstract

Guanine (G)-rich oligonucleotides have attracted considerable interest as therapeutic agents. Two G-rich aptamers were selected against epidermal growth factor receptor (EGFR)-transfected A549 cells, and their G-rich domains (S13 and S50) were identified to account for the binding of parental aptamers. Circular dichroism (CD) spectra showed that S13 and S50 bound to their targets by forming parallel quadruplexes. Their binding, internalization, and antiproliferation activity in cancer and noncancer cells were investigated by flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, and compared with those of nucleolin-binding AS1411 and thrombin-binding aptamer. The two truncated aptamers (S13 and S50) have good binding and internalization in cancer cells and noncancer cells; however, only S50, similar to AS1411, shows potent antiproliferation against cancer cells. Our data suggest that tumor-selective antiproliferation of G-rich oligonucleotides does not directly depend on the binding of the G-rich aptamer to cells.

• Authors: Jun Hu, Zilong Zhao, Qiaoling Liu, Mao Ye, Bingqiang Hu, Jing Wang, Weihong Tan
• Journal: Chemistry, an Asian journal (Chem Asian J) Vol. 10 Issue 7 Pg. 1519-25 (Jul 2015) ISSN: 1861-471X [Electronic] Germany
• PMID: 25864879 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• AGRO 100
• Antineoplastic Agents
• Aptamers, Nucleotide
• Oligodeoxyribonucleotides
• Phosphoproteins
• RNA-Binding Proteins
• nucleolin
• thrombin aptamer
• EGFR protein, human
• ErbB Receptors

Topics

• Adenocarcinoma (drug therapy, metabolism, pathology)
• Adenocarcinoma of Lung
• Antineoplastic Agents (chemistry, pharmacokinetics, pharmacology)
• Aptamers, Nucleotide (chemistry, pharmacokinetics, pharmacology)
• Base Sequence
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• ErbB Receptors (antagonists & inhibitors, metabolism)
• G-Quadruplexes
• Humans
• Lung (drug effects, metabolism, pathology)
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Molecular Sequence Data
• Oligodeoxyribonucleotides (pharmacology)
• Phosphoproteins (metabolism)
• RNA-Binding Proteins (metabolism)