Table 6 Small-molecule compounds that induce ferroptosis to inhibit CSCs
From: Emerging agents that target signaling pathways in cancer stem cells
| Name | Target | Mechanism | Type of cancer | Phase | NCT number (starting time)/publication date | Assessment |
|---|---|---|---|---|---|---|
| Salinomycin | Ferroptosis | Increases the production of lipid peroxidation by blocking iron transport and depleting ferritin; these can specifically kill CSCs | Breast cancer | Preclinical | October, 2017 | Induces neural and muscular toxicity; changing dosages and making chemical modifications may reduce toxicity [159] |
| Ferroptosis | Combined with docetaxel can kill gastric CSCs | Gastric cancer | Preclinical | October, 2017 | ||
| Ironomycin | Ferroptosis | Reduces the number of CSCs in docetaxel-resistant xenograft models | Breast cancer | Preclinical | February 21, 2020 | The potency against CSCs is ten-fold that of salinomycin; may cause nephrotoxicity and hepatotoxicity [160] |
| Ebselen | Ferroptosis | Targets BCSCs by blocking iron in lysosomes | Breast cancer | Preclinical | February 21, 2020 | Induces low toxicity and shows good blood-brain barrier permeability and oral absorption [161] |
| Substituted pyrazoles | February 21, 2020 | Not reported; need studies to prove | ||||
| Benzylisothioureas | February 21, 2020 | Hemoglobinopathy including thalassemia [162] | ||||
| TMZ and CQ | Ferroptosis | Causes glioblastoma stem cells (GSCs) to die through a form of ferroptosis and reduce the self-renewal ability of GSCs | Glioblastoma | Preclinical | August 6, 2018 | TMZ is well tolerated, but may induce hematological toxicity and infection; CQ shows cardiotoxicity [117, 163] |
| DHA | Ferroptosis | Ferroptosis | Lung, colorectal, and breast cancer cells | Preclinical | January, 2020 | Induces neurotoxicity, cardiotoxicity and the toxicity in embryos [164] |
| Apoptosis | Inhibits sphere formation and stem marker (CD133, SOX2, and nestin) expression in glioma CSCs | Gliomas | Preclinical | October, 2014 | ||
| Artesunate | Mitochondrial | Inhibits the stemness of CSCs | Not mentioned | Preclinical | September 2, 2016 | Excellently tolerated, and with low adverse effects [165, 166] |
| Ferroptosis | Induces cell death through ferroptosis | Pancreatic cancer | Preclinical | May 2, 2015 | ||
| Ferumoxytol | Ferroptosis | Selectively kills CSCs (A549 and MDA-MB-231 cells) | Lung cancer and breast cancer | Preclinical | August 26, 2013 | Well tolerated, but intravenous may cause hypersensitivity, hypotension, and gastrointestinal side effects [167,168,169] |
| Sulfasalazine | System Xc− | Inhibits the progression of CSCs overexpressing CD44 | Gastrointestinal cancer | Preclinical | March 8, 2011 | Induces gastrointestinal toxicity, and combed with other drugs, this side effect may be overcome [170] |