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

• Published in: Chemistry, an Asian journal Vol. 10; no. 7; pp. 1519 - 1525
• Main Authors: Hu, Jun, Zhao, Zilong, Liu, Qiaoling, Ye, Mao, Hu, Bingqiang, Wang, Jing, Tan, Weihong
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01.07.2015; Wiley Subscription Services, Inc
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; antiproliferation; aptamers; Aptamers, Nucleotide - chemistry; Aptamers, Nucleotide - pharmacokinetics; Aptamers, Nucleotide - pharmacology; Base Sequence; Cancer; Cell Line, Tumor; Cell Proliferation - drug effects; cell recognition; Chemistry; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - metabolism; G-Quadruplexes; Humans; Lung - drug effects; Lung - metabolism; Lung - pathology; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Molecular Sequence Data; Nucleolin; Oligodeoxyribonucleotides - pharmacology; Phosphoproteins - metabolism; RNA-Binding Proteins - metabolism; cancer; G-quadruplexes; antiproliferation; cell recognition; aptamers
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.201500187

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. Pick and choose: The secondary structure, binding ability, internalization, and antiproliferation activity of two truncated G‐rich aptamers, S13 and S50, were investigated in cancer and noncancer cells, and compared with those of nucleolin‐binding AS1411 and thrombin‐binding aptamer. Tumor‐selective antiproliferation of G‐rich oligonucleotides may not directly depend on the binding of the G‐rich aptamers to cells (see figure).