Investigating the Antiproliferative Activity of High Affinity DNA Aptamer on Cancer Cells |
| |
| Authors: | Harleen Kaur Jasmine J Li Boon-Huat Bay Lin-Yue Lanry Yung |
| |
| Institution: | 1. Department of Chemical and Biomolecular Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore.; 2. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; IDI, Istituto Dermopatico dell’Immacolata, Italy, |
| |
| Abstract: | Vascular endothelial growth factor (VEGF) is an angiogenic mitogen involved in promoting tumor angiogenesis inside the body. VEGF is a key protein required for progression of tumor from benign to malignant phenotype. In this study, we investigated the binding affinity of a previously selected 26-mer DNA aptamer sequence (SL2-B) against heparin binding domain (HBD) of VEGF165 protein. The SL2-B was first chemically modified by introduction of phosphorothioate linkages (PS-linkages). Subsequently, surface plasmon resonance (SPR) spectroscopy and circular dichroism (CD) were used to determine the binding affinity, specificity and to deduce the conformation of PS-modified SL2-B sequence. Finally, antiproliferative activity of the modified SL2-B sequence on Hep G2 cancer cells was investigated. Our results demonstrate a marked enhancement in the biostability of the SL2-B sequence after PS modification. The modified SL2-B sequence also exhibits enhanced antiproliferative activity against Hep G2 cancer cells in hypoxia conditions. In addition, modified SL2-B sequence inhibits the expression of Jagged-1 protein, which is one of the ligands to VEGF linked delta/jagged-notch signaling pathway. |
| |
| Keywords: | |
|
|
