Quercetin Regulates the Expression of Oncogenes through G-quadruplex and Affects the Proliferation and Apoptosis of Tumor Cells
MA Yunqing1, LI Xiaomei1, LIU Xueping1, HAN Yangyang2*, HUANG Weiwei1*
The effect of quercetin on Hep-2 and MCF-7 cells growth and G4-regulated tumor-associated genes expression were investigated by using CCK-8, flow cytometry, immunoblotting, Real-time PCR and in vitro binding assay. The results showed that quercetin significantly inhibited the growth of Hep-2 and MCF-7 cells and induced cell cycle arrest in S phase. Quercetin also induced Hep-2 and MCF-7 cells apoptosis and showed typical apoptotic characteristics such as phosphatidylserine eversion, cell membrane incompletion, chromatin condensation, procaspases activation. Meanwhile, Quercetin significantly inhibited the expression of G4-regulated tumorassociated genes such as c-Myc, KRAS, YY1. Furthermore, Quercetin promoted 27 nucleotide c-Myc promoter G4 (G-quadruplex) formation sequence Pu27 to form stable G4 structures and inhibited binding of the nuclear protein to G4-Pu27. These results indicate that quercetin may inhibit the expression of G4-regulated tumor-associated gene through inducing intracellular G4 structure formation and inhibiting the resolving by G4 helicases, which results into tumor cell growth inhibition and cell apoptosis.
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