Bromelain as a Natural Radiosensitizer in MCF-7 Breast Cancer Cells: Effects on DNA Damage, Clonogenic Survival, and Oxidative Stress

Background and objectives: Radiosensitizers enhance the efficacy of radiotherapy by increasing tumor cell sensitivity to ionizing radiation. Bromelain, a cysteine protease derived from pineapple (Ananas comosus), exhibits anticancer activity and modulates oxidative stress; however, its radiosensitizing potential in breast cancer has not been fully clarified. Methods: MCF-7 breast cancer cells were treated with bromelain (20–80 µg/mL) alone or combined with 2 Gy ionizing radiation. Long-term survival was evaluated using the clonogenic assay. DNA damage was assessed by the cytokinesis-block micronucleus assay. Oxidative stress response was analyzed by measuring superoxide dismutase (SOD) and catalase (CAT) activity. Statistical analysis was performed using one-way ANOVA. Results: Bromelain alone reduced clonogenic survival from 99% in control cells to 71% at 40 µg/mL and 51% at 80 µg/mL. Combined treatment further decreased survival to 35% and 11% at 40 and 80 µg/mL+2 Gy, respectively, compared with 50% in the radiation-only group. Micronucleus frequency increased from 23.7±0.4 in controls to 38.0±1.7 with bromelain alone (80 µg/mL) and to 75.9±0.1 following combined treatment, versus 49.4±0.7 with radiation alone. Antioxidant activity was markedly suppressed, with SOD decreasing from 1.05±0.00 to 0.63±0.01 and CAT from 6.75±0.10 to 1.26±0.09 under combined treatment. Conclusion: Bromelain enhances radiosensitivity in MCF-7 cells by increasing DNA damage, reducing clonogenic survival, and suppressing antioxidant defenses, supporting its potential as a natural adjuvant in breast cancer radiotherapy.