Shikonin Induced Necroptosis via Reactive Oxygen Species in the T-47D Breast Cancer Cell Line

Abstract

Breast cancer, the most common cancer in the women, is the leading cause of death. Necrotic signalingpathways will enable targeted therapeutic agents to eliminate apoptosis-resistant cancer cells. In the presentstudy, the effect of shikonin on the induction of cell necroptosis or apoptosis was evaluated using the T-47D breastcancer cell line. The cell death modes, caspase-3 and 8 activities and the levels of reactive oxygen species (ROS)were assessed. Cell death mainly occurred through necroptosis. In the presence of Nec-1, caspase-3 mediatedapoptosis was apparent in the shikonin treated cells. Shikonin stimulates ROS generation in the mitochondriaof T-47D cells, which causes necroptosis or apoptosis. Induction of necroptosis, as a backup-programmed celldeath pathway via ROS stimulation, offers a new strategy for the treatment of breast cancer.