Polymorphism of human telomeric quadruplex structures

Dai, Jixun; Carver, Megan; Yang, Danzhou

doi:10.1016/j.biochi.2008.02.026

Cited by 390 publications

(443 citation statements)

References 80 publications

(172 reference statements)

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“…[58,90] It is important to note, however, that G-quadruplexes are highly dynamic structures and losses in DNA conformational entropy upon ligand binding might be an important factor in determining specificity. G-quadruplexes that exist as a dynamic mixture of conformations in the unbound state, like the human telomeric sequence, [91] should generally exhibit lower ligand affinities as compared to G-quadruplexes that adopt a single conformation. [58,90] While a large number of G-quadruplex ligands have been reported in the literature, [41,42,46,89,[92][93][94] the cationic porphyrin TMPyP4 (Fig.…”

Section: Some Known G-quadruplex Ligands and Their Activitiesmentioning

confidence: 99%

Targeting G-Quadruplex DNA with Small Molecules

Luedtke¹

2009

Chimia

101

105

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Despite a recent explosion of interest in G-quadruplex DNA, most fundamental questions regarding the possible presence and function of these intriguing structures in vivo remain unanswered. Cell-permeable G-quadruplex specific probes should provide researchers with new tools for studying these alternately folded DNA structures and their potential involvement in gene expression, chromosome stability, viral integration, and recombination. In this review, a survey of the binding affinity, specificity, and biological/pharmacological activities of some well-characterized G-quadruplex ligands is presented along with the potential importance of G-quadruplex DNA in vivo.134 CHIMIA 2009, 63, No. 3 Young AcAdemics in switzerlAnd PArt ii doi:10.2533doi:10. /chimia.2009doi:10. .134 Chimia 63 (2009 Despite a recent explosion of interest in G-quadruplex DNA, most fundamental questions regarding the possible presence and function of these intriguing structures in vivo remain unanswered. Cell-permeable Gquadruplex specific probes should provide researchers with new tools for studying these alternately folded DNA structures and their potential involvement in gene expression, chromosome stability, viral integration, and recombination. In this review, a survey of the binding affinity, specificity, and biological/pharmacological activities of some well-characterized G-quadruplex ligands is presented along with the potential importance of G-quadruplex DNA in vivo.

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Section: Some Known G-quadruplex Ligands and Their Activitiesmentioning

confidence: 99%

Targeting G-Quadruplex DNA with Small Molecules

Luedtke¹

2009

Chimia

101

105

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“…However compounds that stabilize the telomeric G-quadruplex have been shown to inhibit the activity of telomerase and disrupt telomere capping and maintenance, making the human telomeric DNA G-quadruplex also an attractive target for cancer therapeutic intervention (Mergny & Helene, 1998;Riou et al, 2002;Gowan et al, 2001;de Cian et al, 2008). Indeed, the intramolecular telomeric G-quadruplex (Neidle & Parkinson, 2003;Dai et al, 2008) has been considered to be an attractive target for anticancer drug design since quadruplex ligands were found to inhibit telomerase (Sun et al, 1997;Zahler et al, 1991;Zaug et al, 2005). However genomic analyses using several algorithms have revealed that more than 370 000 sequences have the potential to form G-quadruplex structure in the human genome Huppert, 2008).…”

Section: Telomeric G-quadruplexes Are New Targets For Cancer Therapymentioning

confidence: 99%

“…However, this result might be an underestimation of this binding because not all the decays can be detected by this method. In vitro studies have indicated the polymorphic nature of the telomeric G-quadruplex (Dai et al, 2008), and the 3 H-360A ligand may therefore be unable to bind all the G-quadruplex structural conformations. In addition, 3 H-360A is naturally unstable due to progressive radiolysis, so we cannot totally exclude a partial degradation of this G-quadruplex ligand.…”

Section: In Vivo Binding Of G-quadruplex Ligand 360amentioning

confidence: 99%

“…Nevertheless, we cannot at this stage exclude G-quadruplex structure variation and/or the differential regulation of G-quadruplexes during cell cycle progression between normal and cancer cells In vitro studies using oligonucleotides have given some insights into the structural polymorphisms of the G-quadruplex. (Hurley, 2002;Bates et al, 2007;Oganesian & Bryan, 2007;Dai et al, 2008). These polymorphisms and the dynamic equilibrium of telomeric Gquadruplexes, between human normal and cancer cells, may be important for considerations for the design of future therapeutic interventions.…”

Section: The G-quadruplex Ligand 360a Marginally Represses the Prolifmentioning

confidence: 99%

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Differential Effects of the G-Quadruplex Ligand 360A in Human Normal and Cancer Cells

Granotier¹,

Boussin²

2011

DNA Repair and Human Health

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“…Furthermore, K + is essential to fold and stabilize G-quadruplexes (23). Agents that stabilize or target G-quadruplexes may act as anti-tumor agents (24); thus, physiological concentrations of K + are likely to be required for normal cell behavior (25,26). K ascorbate has been proposed as an anti-degenerative agent (27).…”

Section: Introductionmentioning

confidence: 99%

Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

et al. 2016

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Abstract.Ascorbic acid (A) has been demonstrated to exhibit anti-cancer activity in association with chemotherapeutic agents. Potassium (K) is a regulator of cellular proliferation. In the present study, the biological effects of A and K bicarbonate, alone or in combination (A+K), on breast cancer cell lines were evaluated. The survival of cancer cells was determined by sulforhodamine B cell proliferation assay, while analysis of the cell cycle distribution was conducted via fluorescence-activated cell sorting. In addition, the expression of signaling proteins was analyzed upon treatment. The results indicated that there was a heterogeneous response of the different cell lines to A and K, and the best effects were achieved by A+K and A treatment. The interaction between A+K indicated an additive or synergistic effect. In addition, A+K increased the percentage of cells in the sub-G1 phase of the cell cycle, and was the most effective treatment in activating the degradation of poly(adenosine diphosphate-ribose) polymerase-1. In the breast cancer cell line MCF-7, A+K induced the appearance of the 18 kDa isoform of B-cell lymphoma-2-associated X protein (Bax), which is a more potent inducer of apoptosis than the full-length Bax-p21. The effects of A and K on the phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 were heterogeneous. In addition, treatment with K, A and A+K inhibited the expression of nuclear factor-κB. Overall, the results of the present study indicated that K potentiated the anti-tumoral effects of A in breast cancer cells in vitro.

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Polymorphism of human telomeric quadruplex structures

Cited by 390 publications

References 80 publications

Targeting G-Quadruplex DNA with Small Molecules

Targeting G-Quadruplex DNA with Small Molecules

Differential Effects of the G-Quadruplex Ligand 360A in Human Normal and Cancer Cells

Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

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