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G-quadruplex is a special secondary structure of nucleic acids in guanine-rich sequences of genome. G-quadruplexes have been proved to be involved in the regulation of replication, DNA damage repair, and transcription and translation of oncogenes or other cancer-related genes. Therefore, targeting G-quadruplexes has become a novel promising anti-tumor strategy. Different kinds of small molecules targeting the G-quadruplexes have been designed, synthesized, and identified as potential anti-tumor agents, including molecules directly bind to the G-quadruplex and molecules interfering with the binding between the G-quadruplex structures and related binding proteins. This review will explore the feasibility of G-quadruplex ligands acting as anti-tumor drugs, from basis to application. Meanwhile, since helicase is the most well-defined G-quadruplex-related protein, the most extensive research on the relationship between helicase and G-quadruplexes, and its meaning in drug design, is emphasized. [ABSTRACT FROM AUTHOR]

Lysosomes play a key role in regulating cell death in response to cancer therapies, yet little is known on the possible role of lysosomes in the therapeutic efficacy of G-quadruplex DNA ligands (G4L) in cancer cells. Here, we investigate the relationship between the modulation of lysosomal membrane damage and the degree to which cancer cells respond to the cytotoxic effects of G-quadruplex ligands belonging to the triarylpyridine family. Our results reveal that the lead compound of this family, 20A promotes the enlargement of the lysosome compartment as well as the induction of lysosome-relevant mRNAs. Interestingly, the combination of 20A and chloroquine (an inhibitor of lysosomal functions) led to a significant induction of lysosomal membrane permeabilization coupled to massive cell death. Similar effects were observed when chloroquine was added to three new triarylpyridine derivatives. Our findings thus uncover the lysosomal effects of triarylpyridines compounds and delineate a rationale for combining these compounds with chloroquine to increase their anticancer effects. [ABSTRACT FROM AUTHOR]

Guanine-rich sequences in the genomes of herpesviruses can fold into G-quadruplexes. Compared with the widely-studied G3-quadruplexes, the dynamic G2-quadruplexes are more sensitive to the cell microenvironment, but they attract less attention. Pseudorabies virus (PRV) is the model species for the study of the latency and reactivation of herpesvirus in the nervous system. A total of 1722 G2-PQSs and 205 G3-PQSs without overlap were identified in the PRV genome. Twelve G2-PQSs from the CDS region exhibited high conservation in the genomes of the Varicellovirus genus. Eleven G2-PQSs were 100% conserved in the repeated region of the annotated PRV genomes. There were 212 non-redundant G2-PQSs in the 3′ UTR and 19 non-redundant G2-PQSs in the 5′ UTR, which would mediate gene expression in the post-transcription and translation processes. The majority of examined G2-PQSs formed parallel structures and exhibited different sensitivities to cations and small molecules in vitro. Two G2-PQSs, respectively, from 3′ UTR of UL5 (encoding helicase motif) and UL9 (encoding sequence-specific ori-binding protein) exhibited diverse regulatory activities with/without specific ligands in vivo. The G-quadruplex ligand, NMM, exhibited a potential for reducing the virulence of the PRV Ea strain. The systematic analysis of the distribution of G2-PQSs in the PRV genomes could guide further studies of the G-quadruplexes' functions in the life cycle of herpesviruses. [ABSTRACT FROM AUTHOR]