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

Journal

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 244, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2022.114861

Keywords

Ferroptosis; Small-molecule compounds; Lipid peroxidation; Glutathione peroxidase 4; Iron metabolism; Cancer therapy

Funding

  1. National Natural Science Foundation of China
  2. Liao Ning Revitalization Talents Program
  3. [31670359]
  4. [XLYC 1905019]

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This article discusses the interplay between ferroptosis and tumor-related signaling pathways, and comprehensively summarizes the small-molecule compounds that may regulate cancer cell death by inducing ferroptosis, which will shed new light on the development of ferroptosis-related anticancer drugs in the future.
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 car-cinoma cell lines (Huh7, Hep3B and HepG2), and sulfasalazine as a ferroptosis inducer can inhibit the prolif-eration 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 compre-hensively summarizing the small-molecule compounds that may regulate cancer cells death by inducing fer-roptosis which will shed new light on the development of ferroptosis-related anticancer drugs in the future.

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