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Inhibition of myc promoter and telomerase activity and induction of delayed apoptosis by SYUIQ-5, a novel G-quadruplex interactive agent in leukemia cells

Leukemia volume 21, pages 1300–1302 (2007)Cite this article

G-quadruplex structures are involved in many cellular events, including control of gene expression and inhibition of telomerase activity.1, 2 Besides telomeric single-stranded overhang, G-quadruplexes were also present in the promoter or regulatory regions of important oncogene such as c-myc, bcl2, c-Fos and c-ABL.2, 3 C-myc is an important proto-oncogene, which is linked to potentiation of cellular proliferation and to inhibition of differentiation and acts as both a transcriptional activator and repressor. In addition, c-myc plays a function in the apoptotic response.4, 5 Studies demonstrated that the nuclease hypersensitive element (NHEIII) of the c-myc gene promoter was conducive to the formation of G-quadruplex structures.5, 6 Owing to the important function of c-myc, the strategy to target c-myc, especially G-quadruplex structure has emerged as another attractive anti-cancer therapy.

We have tested the formation and stabilization of G-quadruplex of DNA promoted by quindoline derivatives, especially SYUIQ-5 (N′-(10H-indolo (3,2-b) quinolin-11-yl)-N,N-dimethyl-propane-1, 3-diamine) via UV and circular dichroism spectroscopy. Our previous study has proved that SYUIQ-5 could induce the formation of G-quadruplex in telomere structures and induce senescence and telomere shortening in cancer cells.7 C-myc is an important oncogene and is overexpressed in many human malignancies including leukemia. We report here that SYUIQ-5 can also interact with G-quadruplex in the c-myc gene promoter and inhibit its expression. Meanwhile, it can potently induce delayed apoptosis of leukemia cells.

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Acknowledgements

This work was supported by grants from the National Nature Science Foundation of China (30400556, 20472117) and the Fund of Southern China National Research Center for Integrated Biosciences and the specialized Research Fund for the Doctoral program of Higher Education (20060558038).

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  1. Department of Signal Transduction and Anti-Cancer Drug, State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China

    J-N Liu, R Deng, J-F Guo, J-M Zhou, G-K Feng, Y-X Zeng & X-F Zhu

  2. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China

    Z-S Huang & L-Q Gu

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Liu, JN., Deng, R., Guo, JF. et al. Inhibition of myc promoter and telomerase activity and induction of delayed apoptosis by SYUIQ-5, a novel G-quadruplex interactive agent in leukemia cells. Leukemia 21, 1300–1302 (2007). https://doi.org/10.1038/sj.leu.2404652

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