Bioactive nutraceuticals as G4 stabilizers: potential cancer prevention and therapy-a critical review

Abstract

G-quadruplexes (G4) are non-canonical, four-stranded, nucleic acid secondary structures formed in the guanine-rich sequences, where guanine nucleotides associate with each other via Hoogsteen hydrogen bonding. These structures are widely found near the functional regions of the mammalian genome, such as telomeres, oncogenic promoters, and replication origins, and play crucial regulatory roles in replication and transcription. Destabilization of G4 by various carcinogenic agents allows oncogene overexpression and extension of telomeric ends resulting in dysregulation of cellular growth-promoting oncogenesis. Therefore, targeting and stabilizing these G4 structures with potential ligands could aid cancer prevention and therapy. The field of G-quadruplex targeting is relatively nascent, although many articles have demonstrated the effect of G4 stabilization on oncogenic expressions; however, no previous study has provided a comprehensive analysis about the potency of a wide variety of nutraceuticals and some of their derivatives in targeting G4 and the lattice of oncogenic cell signaling cascade affected by them. In this review, we have discussed bioactive G4-stabilizing nutraceuticals, their sources, mode of action, and their influence on cellular signaling, and we believe our insight would bring new light to the current status of the field and motivate researchers to explore this relatively poorly studied arena.

Keywords: Cancer; Chemotherapy; G4; G4 stabilization; Nutraceuticals; Transcriptional regulation.