Ferroptosis-related small-molecule compounds in cancer therapy: Strategies and applications

Ferroptosis is a novel type of regulated cell death which is driven by iron-dependent lipid peroxidation and subsequent plasma membrane ruptures. Since ferroptosis was coined fairly in 2012, the research in the field of ferroptosis has grown at an exponential rate. Several small-molecule drugs have been shown to trigger ferroptosis and decrease tumor growth in the last decade. Sorafenib can induce ferroptosis in human hepatocellular carcinoma cell lines (Huh7, Hep3B and HepG2), and sulfasalazine as a ferroptosis inducer can inhibit the proliferation of a series of cancer cell lines (including HT-1080 fibrosarcoma cells, Calu-1 non-small cell lung cancer cells, etc.) by specifically inhibit cystine transport which mediated by system Xc-. The purpose of this review is discussing the current crosstalk between ferroptosis and tumor-related signaling pathways, as well as comprehensively summarizing the small-molecule compounds that may regulate cancer cells death by inducing ferroptosis which will shed new light on the development of ferroptosis-related anticancer drugs in the future.