Haemin-induced cell death in human monocytic cells is consistent with ferroptosis

• DOI: 10.1016/j.transci.2018.05.028
• Publication Date: 2018-05-29T17:02:20Z
• Authors: Shion Imoto; Mari Kono; Takashi Suzuki; Yukiko Shibuya; Tohru Sawamura; Yuji Mizokoshi; Hirohide Sawada; Ayako Ohbuchi; Katsuyasu Saigo
• Keywords: 0301 basic medicine; Cyclohexylamines; 03 medical and health sciences; Cell Death; THP-1 Cells; Macrophages; Hemin; Humans; Phenylenediamines; Iron Chelating Agents; Reactive Oxygen Species; Monocytes

Iron overload is a major issue for transfusion-dependent patients. Repeated transfusions result in the loading of large amounts of haem-derived iron on macrophages, and the haemin in turn induces cell death and the generation of reactive oxygen species (ROS) in both murine macrophages and human monocytic THP-1 cells. This haemin-induced cell death process has been shown to be iron-dependent. Thus, we hypothesized that haemin-induced THP-1 cell death is a result of ferroptosis, an iron-dependent mechanism of cell death regulation.Human monocytic THP-1 cells were treated with haemin, and haemin-induced cell death and ROS generation were assessed using flow cytometry.Haemin-induced THP-1 cell death showed a necrosis pattern, and treatment with iron chelators suppressed both haemin-induced cell death and ROS generation. Treatment with ferrostatin-1, a ferroptosis inhibitor, suppressed haemin-induced cell death without affecting ROS generation, whereas erastin, a ferroptosis inducer, enhanced both haemin-induced cell death and ROS generation.Our findings support haemin-induced cell death as an example of ferroptosis. Therefore, ferroptosis inhibitors may be useful for the treatment or prevention of transfusion iron overload.