Berberine, an
isoquinoline derivative
alkaloid, has recently been shown to have antitumor activity. The present study aimed to investigate the effects of the concomitant administration of
berberine and radiation on
breast cancer. The effects of
berberine on the radiosensitivity of MCF-7 and MDA-MB-468 cells were evaluated by using cell clonogenic assays. Cells pre-treated with
berberine or
dimethyl sulfoxide (
DMSO) for 24 h were irradiated using a Faxitron Cabinet X-ray System to deliver the indicated doses (0, 1, 2, 3 and 4 Gy). Changes in cell cycle distribution were determined by flow cytometry. γ-H2AX foci were detected by immunofluorescence staining. The levels of Ku70, Ku86 and RAD51
proteins were evaluated by western blot analysis. We observed that
berberine increased the MCF-7 and MDA-MB-468 cell radiosensitivity with cell clonogenic assays. the radiation-induced G2/M cell cycle delay was reduced in the MCF-7 cells pre-teated with
berberine.
Berberine pre-treatment prolonged the persistence of
DNA double-strand breaks in the MCF-7 cell line. In comparison with the control cells, the
protein levels of RAD51 were decreased in the MCF-7 and MDA-MB-468 cells treated with
berberine, and in the cells pre-treated with 15 µM
berberine for 24 h, the level of
RAD51 protein decreased significantly at the indicated time-points (0, 2, 6 and 24 h) following X-ray exposure. In conclusion,
berberine sensitizes human
breast cancer cells to ionizing radiation by inducing cell cycle arrest and the downregulation of the homologous recombination repair
protein, RAD51.
Berberine may be a promising radiosensitizer for the treatment of
breast cancer.