title: Insights into the biomedical effects of carboxylated single-wall carbon nanotubes on telomerase and telomeres.
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.
authors.affiliation: Division of Biological Inorganic Chemistry, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Konggang
authors.initials: K
authors.lastname: Qu
authors.forename: Chuanqi
authors.initials: C
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Jinsong
authors.initials: J
authors.lastname: Ren
authors.forename: Jiasi
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Qu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D054856:G-Quadruplexes / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D037742:Nanotubes, Carbon / Q000737:chemistry*; D011485:Protein Binding; D055550:Protein Stability; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*
chemical_list: D037742:Nanotubes, Carbon; D019098:Telomerase