Insights into the biomedical effects of carboxylated single-wall carbon nanotubes on telomerase and telomeres
- 1 January 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 3 (1), 1-13
- https://doi.org/10.1038/ncomms2091
Abstract
Both human telomeric G-rich and C-rich DNA have been considered as specific drug targets for cancer therapy. However, due to i-motif structure instability and lack of specific binding agents, it remains unclear whether stabilization of telomeric i-motif can inhibit telomerase activity. Single-walled carbon nanotubes (SWNTs) have been reported as the first ligand that can selectively stabilize human telomeric i-motif DNA. Here we report that SWNTs can inhibit telomerase activity through stabilization of i-motif structure. The persistence of i-motif and the concomitant G-quadruplex eventually leads to telomere uncapping and displaces telomere-binding proteins from telomere. The dysfunctional telomere triggers DNA damage response and elicits upregulation of p16 and p21 proteins. This is the first example that SWNTs can inhibit telomerase activity and interfere with the telomere functions in cancer cells. These results provide new insights into understanding the biomedical effects of SWNTs and the biological importance of i-motif DNA.This publication has 59 references indexed in Scilit:
- Making sense of G‐quadruplex and i‐motif functions in oncogene promotersThe FEBS Journal, 2010
- Knocking-Down Cyclin A2 by siRNA Suppresses Apoptosis and Switches Differentiation Pathways in K562 Cells upon Administration with DoxorubicinPLOS ONE, 2009
- Single‐Walled Carbon Nanotubes Binding to Human Telomeric i‐Motif DNA Under Molecular‐Crowding Conditions: More Water Molecules ReleasedChemistry – A European Journal, 2008
- Direct imaging of single-walled carbon nanotubes in cellsNature Nanotechnology, 2007
- Cellular uptake of functionalized carbon nanotubes is independent of functional group and cell typeNature Nanotechnology, 2007
- Functionalized Carbon Nanotubes Are Non-Cytotoxic and Preserve the Functionality of Primary Immune CellsNano Letters, 2006
- Extension of G-quadruplex DNA by ciliate telomeraseThe EMBO Journal, 2006
- Optical Detection of DNA Conformational Polymorphism on Single-Walled Carbon NanotubesScience, 2006
- Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells.1999
- Inhibition of telomerase by G-quartet DMA structuresNature, 1991