title: Mitochondrial dysfunction and nuclear-mitochondrial shuttling of TERT are involved in cell proliferation arrest induced by G-quadruplex ligands.
abstract: G-quadruplex ligands DODC and TMPyP4 have different binding modes to quadruplex structure and cause cell proliferation arrest. Here we showed that DODC was more efficient in cell growth inhibition than TMPyP4. Both G-quadruplex ligands induced nuclear-cytoplasmic shuttling and accumulation of TERT in mitochondria. This effect was not fully dependent on cellular oxidative stress. DODC induced robust cell apoptosis by perturbing mitochondrial function intensively. Overexpression of TERT could not counteract the effects of DODC on mitochondrial respiratory function. Taken together, our results suggest that interference of mitochondrial function by DODC is one of main targets for its anti-tumor ability.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
authors.forename: Xin-Ying
authors.initials: XY
authors.lastname: Zhuang
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002232:Carbocyanines / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D049109:Cell Proliferation; D054856:G-Quadruplexes; D015870:Gene Expression; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000187:drug effects; D011166:Porphyrins / Q000494:pharmacology*; D021381:Protein Transport; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002232:Carbocyanines; D008024:Ligands; D011166:Porphyrins; C018919:3,3'-diethyloxadicarbocyanine; C021096:tetra(4-N-methylpyridyl)porphine; C509186:TERT protein, human; D019098:Telomerase