Berberine Sensitises Breast Cancer Cells to Radiation via the Attenuation of DNA Ligase III

Abstract

Berberine (BBR) is an isoquinoline alkaloid with a variety of biological activities, including anti-microbial and anti-tumoral activities. However, the cellular targets of BBR and the roles of BBR in the radiosensitivity of breast cancer cells are not well defined. In this study, we investigated the effects of BBR on the radiosensitivity of BT549 triple-negative breast cancer cells. Through RNA-seq results, we found that BBR significantly down-regulated the expression of DNA ligases. The results of western blot and comet assay confirmed that BBR attenuated DNA ligase III (LIGIII) expression and caused DNA damage in a dose-dependent manner. The results of electron microscopy showed that BBR decreased mitochondrial copies and induced mitochondrial autophagy. Clonal formation analysis showed that BBR sensitised breast cancer cells to irradiation. The genetic complementation and interference assays showed that the effect of BBR on the radiosensitivity of BT549 breast cancer cells is dependent on the expression of LIGIII. These results contribute to the understanding of the effects of BBR on cellular DNA repair and the clinical application of BBR in breast cancer therapy.