An evaluation cascade for G-quadruplex telomere targeting agents in human cancer cells.
The targeting of telomerase and telomere maintenance in human cancer cells can be achieved by small molecules that induce the 3'single-stranded ends of telomeric DNA to fold up into four-stranded quadruplex structures that inhibit the action of the telomerase enzyme complex. In this chapter, we describe a series of biochemical, biophysical, and cellular assays that are used to evaluate the activity of new compounds, and so assess whether they are suitable for examination in xenograft models of human cancer. These assays evaluate quadruplex stabilisation properties, short- and long-term cell viability, telomerase enzymatic activity, cellular senescence, and telomere length changes.
Gunaratnam
Mekala
M
The Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, London, UK.
Neidle
Stephen
S
D001483:Base Sequence; D055162:Biocatalysis; D001688:Biological Products / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000473:pathology*; D012235:Rhodamines / Q000494:pharmacology; D013194:Staining and Labeling; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016615:Telomere / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D001616:beta-Galactosidase / Q000378:metabolism
D001688:Biological Products; D004791:Enzyme Inhibitors; D012235:Rhodamines; C022027:lissamine rhodamine B; D004247:DNA; D019098:Telomerase; D001616:beta-Galactosidase