Preferential stabilization of c-MYC and BCL-2 promoter G-quadruplexes by a natural betaine-type alkaloid

Abstract

In this study, we demonstrate for the first time that the betaine-type alkaloid Lycobetaine ( LYC ) preferentially binds to c-MYC and BCL-2 promoter G-quadruplexes (G4s). Biophysical experiments including absorption titrations, CD melting and NMR studies showed that LYC had the ability to bind and stabilize both c-MYC and BCL-2 G4s through an end-stacking mode. Additional biological assays including RT-PCR and Western blotting indicated that LYC simultaneously inhibited the expression of c-MYC and BCL-2 oncogenes in A549/DDP cells, which thereby led to cell cycle arrest, apoptosis, as well as inhibition on cell proliferation and migration. Taken together, these results revealed a new potential anticancer mechanism of LYC with potential application of LYC in drug-resistant cancers. • The betaine-type alkaloid lycobetaine ( LYC ) preferentially binds to c-MYC and BCL-2 promoter G-quadruplexes. • LYC simultaneously inhibits the expression of c-MYC and BCL-2 oncogenes. • This study uncovers a new potential anticancer mechanism of LYC . • This work extended the application of LYC in drug-resistant cancers.