Resistance to G-Quadruplex Ligands

As any potential therapeutic agents, the biological effect of G-quadruplex ligands may be overcome by the appearance of acquired-resistance phenotypes or to be lowered by the intrinsic expression of proteins already known to be associated with resistance to anticancer agents. The selection as well as the analysis of resistant cells is a well-known strategy to obtain information on the mechanisms of drug inactivation and on their target proteins, if a modification of their expression, or a mutation can be related to the resistance phenotype. 

The proteins involved in the multidrug-resistance phenotype, including MDRl, MRPs, or BCRP genes products, are the first potential candidates to 

G-quadruplex ligands induced a telomere dysfunction that is characterized by the appearance of anaphase bridges and telomere end-to-end fusions in treated cells. The induction of short-term apoptosis is also frequently observed. The telomere dysfunction may appear before any evidence of telomere shortening by 

This situation argues that 12459-resistant cell lines may present potential modifications of intracellular targets involved in the control of the drug-induced senescence and/or apoptosis. 

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