Development of novel application of 3,3'-diindolylmethane: sensitizing multidrug resistance human breast cancer cells to γ-irradiation.

CONTEXT: Multidrug resistance (MDR) is known as a major obstacle to effective cancer therapy. The effects of irradiation on MDR in cancer cells had rarely been reported.

OBJECTIVE: The effect of 3,3'-diindolylmethane (DIM) sensitizing MDR human breast carcinoma to γ-irradiation was investigated.

MATERIALS AND METHODS: MCF-7/ADR cells were exposed to different concentrations of DIM (0-30 μM) for 48 or 2 h before IR (γ-Co(60), 10 Gy, room temperature) then cultured for 48 h. Cell survival was determined by MTT assay. Intracellular reactive oxygen spices (ROS) induced by DIM (20 and 30 μM, 2 h before irradiation) was measured by flow cytometry. Propidium iodide staining assay was used for cell cycle distribution studies; cell apoptosis was measured by flow cytometry and confocal microscopy.

RESULTS: DIM (20 and 30 μM, 2 h before irradiation) sensitized MCF-7/ADR cells to IR with survival rates decreased from 100% to 79% and 63%, respectively. DIM combined with γ-radiation demonstrated that the activity of G2/M phase cell cycle arresting with percentages enhanced from 9% to 49% and 52%. DIM can increase intracellular ROS generation by 1.45- and 1.55-times compared to control group. Significantly enhanced radiation-induced apoptosis by DIM was also observed.

DISCUSSION AND CONCLUSION: These data provide a rationale for the use of DIM as a promising radio-sensitizer to MDR cancer cells.