Insights into the biomedical effects of carboxylated single-wall carbon nanotubes on telomerase and telomeres
Date
2012
Authors
Chen, Y.
Qu, K.
Zhao, C.
Wu, L.
Ren, J.
Wang, J.
Qu, X.
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Journal article
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Nature Communications, 2012; 3(9):1074-1-1074-13
Statement of Responsibility
Yong Chen, Konggang Qu, Chuanqi Zhao, Li Wu, Jinsong Ren, Jiasi Wang & Xiaogang Qu
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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.
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© 2012 Macmillan Publishers Limited. All rights reserved.