Inhibition of Cell Proliferation by Quindoline Derivative (SYUIQ-05) through its Preferential Interaction with c-myc Promoter G-Quadruplex

• Published in: Journal of medicinal chemistry Vol. 54; no. 16; pp. 5671 - 5679
• Main Authors: Ou, Tian-Miao, Lin, Jing, Lu, Yu-Jing, Hou, Jin-Qiang, Tan, Jia-Heng, Chen, Shu-Han, Li, Zeng, Li, Yan-Ping, Li, Ding, Gu, Lian-Quan, Huang, Zhi-Shu
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 25.08.2011
• Subjects: Base Sequence; Blotting, Western; Cell Line, Tumor; Cell Proliferation - drug effects; Cellular Senescence - drug effects; Diamines - chemistry; Diamines - metabolism; Diamines - pharmacology; DNA, Neoplasm - chemistry; DNA, Neoplasm - genetics; DNA, Neoplasm - metabolism; G-Quadruplexes; Gene Expression Regulation, Neoplastic; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; HeLa Cells; HL-60 Cells; Humans; Inhibitory Concentration 50; K562 Cells; Microscopy, Confocal; Molecular Structure; NM23 Nucleoside Diphosphate Kinases - genetics; NM23 Nucleoside Diphosphate Kinases - metabolism; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Quinolines - chemistry; Quinolines - metabolism; Quinolines - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Telomerase - genetics; Telomerase - metabolism; Telomere - drug effects; Telomere - genetics
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm200062u

G-Quadruplex is a special DNA secondary structure and present in many important regulatory regions in human genome, such as the telomeric end and the promoters of some oncogenes. Specially, different forms of G-quadruplexes exist in telomeric DNA and c-myc promoter and play important roles in the pathway of cell proliferation and senescence. The effects of G-quadruplex ligands for either telomeric or c-myc G-quadruplex in vitro have been widely studied, but the specificity of these effects in vivo is still unknown. In the present research, various experiments were carried out to study the effect of G-quadruplex ligand SYUIQ-05 on tumor cell lines and the mechanism of this effect. Our results showed that it preferred to bind with G-quadruplex in c-myc and had rather insignificant effect on G-quadruplex in telomere. Therefore, it is possible that this compound had its antitumor activity for cancer cells mainly through its interaction with c-myc quadruplex.