Harnessing Gingerols to Stabilize Telomeric Repeat-Containing RNA G-Quadruplexes and Manage Cancer

The active ingredients of ginger ( Zingiber officinale ) are 6-gingerol, 8-gingerol, and 10-gingerol. Ginger is reported to be an antioxidant, anticancer, and anti-inflammatory agent because of its bioactive metabolites. The 3 gingerols share a standard ring structure with different side chains. The maintenance of telomeric length by telomerase is a major issue in almost all cancers. Targeting TERRA G4 could provide a method to inhibit telomerase activity. Molecular docking, molecular dynamics simulations, molecular mechanics Poisson–Boltzmann surface area, principal component analysis, and free energy landscape analysis were performed to evaluate gingerol–TERRA G4 interactions, the extent and stability of these interactions, and the binding free energy and stability of the complexes of the 3 gingerols with TERRA G4. The results revealed that 10-gingerol has superior binding and stabilizing potential for TERRA G4 structures. These findings suggest that TERRA G4 could be a promising therapeutic target for cancer and that 10-gingerol may serve as a potential anticancer lead compound. Further in vitro and in vivo studies to determine the effective dose and toxicity are necessary to evaluate its safety and efficacy.