title: 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 signaling pathways will enable targeted therapeutic agents to eliminate apoptosis-resistant cancer cells. In the present study, the effect of shikonin on the induction of cell necroptosis or apoptosis was evaluated using the T-47D breast cancer 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 mediated apoptosis was apparent in the shikonin treated cells. Shikonin stimulates ROS generation in the mitochondria of T-47D cells, which causes necroptosis or apoptosis. Induction of necroptosis, as a backup-programmed cell death pathway via ROS stimulation, offers a new strategy for the treatment of breast cancer.
authors.affiliation: Cancer Research Laboratory, Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Iran E-mail : karamitf@modares.ac.ir.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Shahsavari
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Karami-Tehrani
authors.forename: Siamak
authors.initials: S
authors.lastname: Salami
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D009336:Necrosis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; C016101:shikonin; D053148:Caspase 3