A Protein Biosynthesis Machinery Strategy for Identifying P53PTC‐Rescuing Compounds as Synergic Anti‐Tumor Drugs

• Published in: ChemistrySelect (Weinheim) 2018-10, Vol.3 (39), p.11048-11053
• Main Authors: Zhou, Jingjing, Qiu, Chengbin, Pi, Ni, Li, Sicong, Cheng, Xiyao, Zhang, Lei, Chen, Yao, Huang, Yongqi, Sun, Yuhui, Su, Zhengding
• Format: Article
• Language: English
• Subjects: aminoglycoside; doxorubicin; green fluorescent protein; p53; premature termination codons
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201802635

The readthrough of premature termination codons (PTCs) is a promising strategy for curing PTC‐causing diseases. In cancers, the p53 anti‐tumor activity is often disabled by forming premature terminated p53 protein (p53PTC). Currently, there are lack of p53PTC‐rescuing drugs. Herein we designed a feasible strategy for identifying p53PTC‐rescuing compounds using protein biosynthesis machinery in E. coli cells and the lung cancer H1299 cells both harboring p53PTC‐GFP fusion protein expression cassettes. Rescued p53PTC protein enabled a GFP‐tag for fluorescence spectroscopic measurements. Our data revealed that the aminoglycoside G418 not only efficiently rescued p53PTC in H1299 cells, but also synergistically enhanced the efficacy of antitumor drug doxorubicin. Our work gave an insight into the discovery of p53PTC‐rescuing drugs for cancer therapy. In cancers, the p53 anti‐tumor activity is often disabled by forming premature terminated p53 protein (p53PTC). A feasible strategy was provided for identifying p53PTC‐rescuing compounds. Furthermore, our study found that the aminoglycoside G418 not only efficiently rescued p53PTC in H1299 cells, but also synergistically enhanced the efficacy of antitumor drug doxorubicin. Our work gave an insight into the discovery of p53PTC‐rescuing drugs for cancer therapy.