Therapeutic Fractional Doses of Ionizing Radiation Promote Epithelial-Mesenchymal Transition, Enhanced Invasiveness, and Altered Glycosylation in MCF-7 Breast Cancer Cells

Abstract

The clinical outcome of radiation therapy is restricted due to the acquired radio-resistance of a subpopulation of tumour cells that may cause tumour relapse and distant metastasis. While the effects of ionizing radiation (IR) such as DNA damage and cell stress are well-documented, the potential role of IR in inducing invasive potential in cancer cells has not been broadly studied, therefore we aimed to investigate it in this study. MCF-7 cells irradiated with 0 Gy (control) or 2 Gy X-ray therapeutic doses of IR were assessed for cell viability, percentage of apoptotic cells, and reactive oxygen species (ROS) levels, DNA fragmentation, Matrigel invasion, assessment of epithelial–mesenchymal transition (EMT) markers and Helix pomatia agglutinin (HPA) binding at 30 min, 4- or 24-h post-IR. Reduction in cell viability, increase in apoptotic cells, ROS positive cells, and DNA fragmentation were observed, while functional invasiveness and EMT were exacerbated together with altered glycosylation in MCF-7 cells irradiated with 2 Gy X-ray compared to control cells. These findings indicate that despite the detrimental effects of 2 Gy X-ray IR on MCF-7 cells, a subpopulation of cells may have gained increased invasive potential. The exacerbated invasive potential may be attributed to enhanced EMT and altered glycosylation. Moreover, deregulation of transforming growth factor-beta (TGF-β) following IR may be one of the elements responsible for these changes, as it lies in the intersection of these invasion-promoting cell processes.