Journal of Chinese Pharmaceutical Sciences ›› 2019, Vol. 28 ›› Issue (5): 289-297.DOI: 10.5246/jcps.2019.05.029

• Original articles •     Next Articles

Berberine enhances the activity of Sunitinib by targeting telomere G-quadruplex

Haitao Hou1#, Zibing Song1#, Jieqin Ding1, Dengguo Wei1, Sheng Hu2, Qianqian Zhai1*, Xiali Yue1*   

  1. 1. Department of Chemistry, College of Science, Huazhong Agricultural University, Wuhan 430070, China
    2. Hubei Cancer Hospital, Wuhan 430079, China
  • Received:2019-03-07 Revised:2019-03-30 Online:2019-05-31 Published:2019-04-05
  • Contact: Tel.: +86-027-87284018, E-mail:;
  • Supported by:

    Huazhong Agricultural University Scientific & Technological Self-innovation Foundation (Grant No. 2015RC013); The Fundamental Research Funds for the Central Universities (Grant No. 2662017PY113, 2662015PY208, 2662015BQ048); 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.


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 percentageof 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.

Key words: Telomere G-quadruplex, Sunitinib, Berberine, Synergistic effects

CLC Number: 


Table S1. DNA sequences used in the FRET melting assay




Figure S1 The cytotoxic effect on A549 cancer cells of sunitinib or berberine. The cells were treated with sunitinib for 24 h or 48 h. The cells were treated with berberine for 48 h.  


Table S2. The combination effects of berberine and sunitinib on A549 cancer cells.