ABSTRACT
ABSTRACT: Evidence is growing that potassium channels play important roles in the development and growth of human cancer, including breast cancer. In this study, we investigated the effect of 4-aminopyridine (4-AP), an inhibitor of voltage-gated potassium channels, on the growth of human breast cancer MCF-7 cells, with an attempt to know whether pre-arresting tumor cells at a certain phase could affect anti-proliferative activities of cell cycle-specific drugs, and found that 4-AP significantly inhibited the cell proliferation and induced apoptosis in a dose-dependent manner. 4-AP also significantly blocked the cell cycle in G1 phase at 1 mmol/l, and induced mainly S phase arrest at 5 and 10 mmol/l. Further studies exhibited strong synergistic action between 4-AP (5 mmol/l) and S phase-specific drug 5-FU, and antagonistic action between 4-AP (5 mmol/l) and G2/M phase-specific drug paclitaxel, indicating that cell cycle parameters should be considered in the combination therapy involving cell cycle-specific agents.
