Effects of Dimeric Bisbenzimidazoles and Ionizing Radiation on MCF-7 Breast Cancer Stem Cells

摘要

—This study aimed to determine how to eliminate and/or increase the radiosensitivity of a population of cancer stem cells that are responsible for radioresistance in malignant neoplasms. The single and combined effects of γ-radiation at a dose of 4 Gy and dimeric bisbenzimidazoles of the DB( n ) series on the cancer stem cells have been studied using the MCF-7 human breast cancer cell line. The DB( n ) molecules contain n (five or seven) methylene groups in the linker between two benzimidazoles. It has been shown that DB(5) significantly reduces the relative and absolute numbers of the cancer stem cells by factors of 5.8 and 7.5, respectively, compared to the control ( p = 0.001 in both cases), and DB(7) reduces the above cell numbers by factors of 3.6 ( p = 0.003) and 5.2 ( p = 0.004), respectively. Irradiation leads to an increase of the relative and absolute numbers of cancer stem cells by factors of 1.7 and 1.6 ( p < 0.05) compared to the control, respectively. The combined effects of DB(5, 7) and ionizing radiation led to a significant decrease in the relative number of cancer stem cells by factors of 8.2 and 4.1, respectively, compared to only the single irradiation ( p = 0.003 and p = 0.004). Even more pronounced outcomes of the combined action of DB(5, 7) and radiation have been found with regard to the absolute number of cancer stem cells, which decreases by factors of 16.6 and 14.1, respectively, compared to those after only single irradiation ( p = 0.006 in both cases). The combined effect of DB(5, 7) and ionizing radiation led to the inhibition of the radiation-induced epithelial-mesenchymal transition as shown by the expression of vimentin, which is one of the markers of this process that plays an important role in the formation of cancer stem cells pool.