Radiosensitization effects of berberine on human breast cancer cells.
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.
Department of Oncology, Qilu Hospital, Shandong University School of Medicine, Jinan, PR China.
Jing
J
Wang
Qiao
Q
Liu
Qifeng
Q
Yang
D034961:Antigens, Nuclear / Q000378:metabolism; D001599:Berberine / Q000494:pharmacology*; D001943:Breast Neoplasms; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D000072200:Ku Autoantigen; D061986:MCF-7 Cells; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D011838:Radiation-Sensitizing Agents; D001599:Berberine; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen