Cucurbitacin B causes increased radiation sensitivity of human breast cancer cells via G2/M cell cycle arrest

Purpose. to explore the effects of cucurbitacin b on the radiation survival of human breast cancer cells and to elucidate the cellular mechanism of radiosensitization if any. materials and methods. human breast carcinoma cell lines were treated with cucurbitacin b before irradiation with 0-10gy of 137cs gamma rays. the effect of cucurbitacin b on cell-survival following irradiation was evaluated by colony-forming assay. cell cycle distributions were investigated using flow cytometry. real-time pcr and western blots were performed to investigate the expression of cell cycle checkpoints. results. cucurbitacin b inhibited breast cancer cell proliferation in a dose-dependent manner. only mda-mb-231 and mcf7:5c cells but not skbr-3 cells were radiosensitized by cucurbitacin b. flow cytometric analysis for dna content indicated that cucurbitacin b resulted in g2/m arrest in mda-mb-231 and mcf7:5c but not skbr-3 cells. moreover,real-time pcr and western blot analysis demonstrated upregulated p21 expression before irradiation,a likely cause of the cell cycle arrest. conclusion. taken together,these findings suggest that cucurbitacin b causes radiosensitization of some breast cancer cells,and that cucurbitacin b induced g2/m arrest is an important mechanism. therefore,combinations of cucurbitacin b with radiotherapy may be appropriate for experimental breast cancer treatment. copyright © 2012 suwit duangmano et al.