Abstract: Objective   To investigate the anti-tumor effect of brucine and strychnine based on their blockage of hERG channels.   Methods  The vector-transfected and hERG-transfected CHO cells were constructed by Lipofection and selective medium. After treated with brucine and its structural analogues for 24 h, 48 h, and 72 h, the effect in cell proliferation in cancer cells were evaluated by using CCK8 assay. After treated with brucine and its structural analogues for 48 h, the effect in cell proliferation in hERG-transfected CHO cells were evaluated by using CCK8 assay, and the vector-transfected CHO cells were as control. Flow cytometry was used to detect the cell cycle arrest of brucine and strychnine on HT29 and A549 cells. Western blot was used to detect the levels of hERG expression in HT29, PC9, and A549 cells.   Results   Brucine and strychnine time and dose-dependently inhibited the proliferation of HT29, PC9, and A549 cell lines, and the inhibitory potency was positively correlated with the expression level of hERG protein. Faint anti-proliferation activity was detected at high concentration for brucine N-oxide and strychnine N-oxide which showed weak inhibitory effect on hERG channel and tumor cell only at high concentration. Furthermore, brucine induced more growth suppression on the hERG-transfected CHO cells, when compared with vector-transfected CHO cells. Brucine and strychnine induced G0/G1cell cycle arrest in HT29 cells, and showed no significant effect on the cell cycle of A549 cells. Brucine showed no significant effects on hERG protein expression in the three cell lines.    Conclusions    Brucine and strychnine displayed their anti-tumor effect may through blocking hERG channels. This study may provide important clues for using the potential pharmacologic effects of hERG inhibitors in cancer treatment.

Key words: Nux Vomica; ,  , Anti-tumor; ,  , hERG expression; ,  ,  hERG blocker