Bromelain augments ionizing radiation sensitivity in breast cancer cells: A synergistic approach

Radiation-sensitizing agents, such as Bromelain (pineapple extract) have been shown to significantly impact cancer cell cycle arrest. This study investigates the anticancer properties of Bromelain on MCF-7 breast cancer cell line under both two-dimensional (2D) and three-dimensional (3D) culture conditions. Bromelain enzyme was initially applied at concentrations of 75, 96, and 115 μg/ml to sensitize the MCF-7 cells under both 2D and 3D culture conditions. Following treatment, the cells were irradiated with doses of 2, 4, and 6 Gy. The synergistic effects of bromelain enzyme treatment and gamma irradiation on MCF-7 cells were assessed using the MTT assay, neutral red uptake assay, alkaline comet assay, nitric oxide (NO) release measurement, catalase activity assay, reduced glutathione quantification, and caspase 3 assay. Data were analyzed and presented as Mean ± SD using GraphPad InStat software V. 8. The MTT assay indicated that the combination of bromelain and ionizing radiation have synergistic effects compared to cells treated with 2 Gy of X-ray alone. The results from of the MTT assay indicated showed that 75 μg/ml of bromelain did not induce exhibit significant cytotoxicity. Consistent with the MTT assay results, the Neutral red uptake assay demonstrated increased mortality in MCF-7 cells following treatment with both bromelain and ionizing radiation. Additionally, treatment with bromelain and ionizing radiation resulted in elevated levels of released NO, GSH content, and catalase enzyme activity compared to cells treated with bromelain alone. Furthermore, the Combination of ionizing radiation and bromelain synergistically enhanced caspase-3 enzyme activity and increased the number of necrotic and apoptotic cells compared to treatment with bromelain alone. Bromelain's capacity to induce apoptosis and enhance radio-sensitization offers promising potentialfor improving cancer treatment outcomes. By promoting programmed cell death and increasing the sensitivity of cancer cells to radiation, bromelain could contribute to more effective treatment regimens while potentially reducing the adverse effects associated with more aggressive therapies.