Natural compounds from Juncus plants interacting with telomeric and oncogene G-quadruplex structures as potential anticancer agents

Aiming at discovering novel, putative anticancer drugs featuring low-to-null side effects, natural compounds isolated from Juncaceae were studied here for their ability to target G-quadruplex structures originating from cancer-related telomeric and oncogene DNA sequences. Particularly, various dihydrophenanthrene, benzocoumarin and dihydrodibenzoxepin derivatives were firstly screened by the affinity chromatography-based G4-CPG assay, and the compound with the highest affinity and selectivity for G-quadruplexes (named J10) was selected for further studies. Fluorescence spectroscopy and circular dichroism experiments corroborated its capability to selectively recognize and stabilize G-quadruplexes over duplex DNA, also showing a preference for parallel G-quadruplexes. Molecular docking proved that the selective G-quadruplex interactions over duplex interactions could be due to the ability of J10 to bind to the grooves of the telomeric and oncogene G-quadruplex structures. Finally, biological assays demonstrated that J10 induces significant antiproliferative effects on human leukemia cells, with no relevant effects on healthy human fibroblasts. Interestingly, J10 exerts its antiproliferative action on tumor cells by activating the apoptotic pathway.

Automated summary

This study focused on natural compounds from Juncaceae for potential anticancer drugs targeting cancer-related G-quadruplex structures. Compound J10 was found to selectively recognize and stabilize G-quadruplexes, leading to significant antiproliferative effects on human leukemia cells without impacting healthy human fibroblasts. Further research indicated that J10 activates the apoptotic pathway in tumor cells, highlighting its potential as a novel anticancer agent.