Recent studies have shown that Ro 90-7501, a drug initially developed to inhibit amyloid β42 fibril formation in Alzheimer's disease, can sensitize cervical cancer cells to radiation, likely by impairing DNA double-strand break (DSB) repair. This study aims to assess the radio-sensitizing potential of Ro 90-7501 in breast cancer and normal fibroblast cell lines, focusing on its impact on DNA DSB repair to optimize radiotherapy (RT) efficacy.

Two breast cancer cell lines (MDA-MB-231, MCF7) and one normal skin fibroblast cell line (GM03652) were used in this study. Cells were treated with Ro 90-7501 (1, 3 and 10 μM), with or without 2 Gy of ionizing radiation. Cell viability, proliferation, and cytotoxicity were evaluated using MTT and Trypan Blue assays. DNA damage and repair were analyzed by quantifying γH2AX and pATM foci at 0, 10 minutes, 1 hour, 4 hours, and 24 hours post-irradiation using immunofluorescence. Clonogenic assay was conducted to assess cell survival.

Ro 90-7501 reduced viability and proliferation in breast cancer cells (p-value < 0.01) without affecting normal fibroblasts (p-value > 0.05). Following 2 Gy irradiation, Ro 90-7501 induced an increase in residual γH2AX foci at 24 hours post-treatment (p-value < 0.001) and significantly reduced pATM foci at 10 minutes and 1 hour (p-value < 0.01) in both cancer cell lines. Clonogenic assay revealed a significant reduction in colony formation in MCF-7 cells with 3 μM and 10 μM of Ro 90-7501 (p-value < 0.01), while no effect was observed in MDA-MB-231 cells or normal fibroblasts (p-value > 0.05).

In conclusion, Ro 90-7501 exhibits radio-sensitizing effects on breast cancer cell lines at both the molecular and cellular levels, with minimal impact on normal cells. These findings suggest that Ro 90-7501 has potential as a radio-sensitizer, capable of enhancing tumor response while minimizing effects on normal tissue.