Gingerenone A induces ferroptosis in colorectal cancer via targeting suppression of SLC7A11 signaling pathway

作者：Hongyu Xiao, Chen Chen, Xin Yuan, Limei Yang, Yun Zheng, Yuan Jin, Song Huang, Jian Liang, Shengliang Yuan, Meifen Li, Junyan Wang · 发表于：Biomedicine & Pharmacotherapy · 年份：2024 · DOI：10.1016/j.biopha.2024.117529 · 被引用次数：16 · 研究领域：Ferroptosis and cancer prognosis、Immune cells in cancer、Ginger and Zingiberaceae research

Colorectal cancer (CRC) is one of the most common and fatal diseases, yet effective therapeutic drugs are lacking in clinical settings. Gingerenone A (GA) is an active compound derived from ginger, has demonstrated anti-tumor properties. However, the efficacy of GA against CRC and its primary mechanism of action remain unclear. MTT assay and colony formation assay were employed to evaluate cell viability. Transwell assays were utilized to assess the migratory and invasive capabilities of the cells. The effects of GA on ferroptosis related proteins were analyzed using Western blot. Levels of glutathione (GSH), malondialdehyde (MDA), Fe 2+ , and 4-hydroxynonenal (4-HNE) levels were measured with a biochemical index determination kit. Cellular reactive oxygen species (ROS) were quantified using flow cytometry. CETSA, pull-down, and co-immunoprecipitation (Co-IP) assays confirmed the interactions between GA and SLC7A11, as well as the ubiquitination promoted by SLC7A11. A xenograft mouse model was employed to validate the anticancer effect of GA in vivo . We observed that GA significantly suppressed proliferation in human CRC cells. Additionally, GA treatment inhibited the migration, invasion, and colony formation of CRC cells. Subsequently, through the use of specific inhibitors, we discovered that the suppression of CRC cells by GA was dependent on ferroptosis rather than autophagy or apoptosis. Previous research has demonstrated that GA treatment significantly triggers ferropt...