G-quadruplexes are stable secondary structures formed with guanine rich sequences,which are widely distributed in genome.Chemical compounds stabilizing G-quadruplexes exhibited inhibition on tumor cells.However,the fe...G-quadruplexes are stable secondary structures formed with guanine rich sequences,which are widely distributed in genome.Chemical compounds stabilizing G-quadruplexes exhibited inhibition on tumor cells.However,the feasibility of G-quadruplex structures as drug targets needs to be validated.In this study,Sunitinib,an antitumor drug targeting tyrosine kinases was found to stabilize telomere G-quadruplex.The stabilization was further enhanced by the combined usage with Berberine,an isoquinoline alkaloid.Circular dichroism spectra showed the synergistic effect comes from inducing the conformation conversion of telomere G-quadruplex.The combination of Berberine with Sunitinib resulted in 1.7-fold enhancement in cell apoptosis rate with the percentage of apoptotic cells reaching about 70%.The confocal microscopy immunofluorescence images showed the combination of Berberine and Sunitinib induced the formation of G-quadruplex at the telomere in A549 cancer cells.This study suggested that more clinic drugs could work by targeting G-quadruplex structures.展开更多
基金Huazhong Agricultural University Scientific&Technological Self-innovation Foundation(Grant No.2015RC013)The Fundamental Research Funds for the Central Universities(Grant No.2662017PY113,2662015PY208,2662015BQ048)+2 种基金National Natural Science Foundation of China(Grant No.21502060,21708011)Open fund of The State Key Laboratory of Bio-organic and Natural Products Chemistry,CAS(Grant No.SKLBNPC16343)Open fund of Beijing National Laboratory For Molecular Sciences
文摘G-quadruplexes are stable secondary structures formed with guanine rich sequences,which are widely distributed in genome.Chemical compounds stabilizing G-quadruplexes exhibited inhibition on tumor cells.However,the feasibility of G-quadruplex structures as drug targets needs to be validated.In this study,Sunitinib,an antitumor drug targeting tyrosine kinases was found to stabilize telomere G-quadruplex.The stabilization was further enhanced by the combined usage with Berberine,an isoquinoline alkaloid.Circular dichroism spectra showed the synergistic effect comes from inducing the conformation conversion of telomere G-quadruplex.The combination of Berberine with Sunitinib resulted in 1.7-fold enhancement in cell apoptosis rate with the percentage of apoptotic cells reaching about 70%.The confocal microscopy immunofluorescence images showed the combination of Berberine and Sunitinib induced the formation of G-quadruplex at the telomere in A549 cancer cells.This study suggested that more clinic drugs could work by targeting G-quadruplex structures.
