Insights into the biomedical effects of carboxylated single-wall carbon nanotubes on telomerase and telomeres

Yong Chen, Konggang Qu, Chuanqi Zhao, Li Wu, Jinsong Ren, Jiasi Wang and Xiaogang Qu ()
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Yong Chen: State Key Laboratory of Rare Earth Resource Utilization, Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences
Konggang Qu: State Key Laboratory of Rare Earth Resource Utilization, Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences
Chuanqi Zhao: State Key Laboratory of Rare Earth Resource Utilization, Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences
Li Wu: State Key Laboratory of Rare Earth Resource Utilization, Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences
Jinsong Ren: State Key Laboratory of Rare Earth Resource Utilization, Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences
Jiasi Wang: State Key Laboratory of Rare Earth Resource Utilization, Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences
Xiaogang Qu: State Key Laboratory of Rare Earth Resource Utilization, Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences

Nature Communications, 2012, vol. 3, issue 1, 1-13

Abstract: 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.

Date: 2012
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DOI: 10.1038/ncomms2091

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