Small-Molecule Ferroptotic Agents with Potential to Selectively Target Cancer Stem Cells
| Autor: | Samkeliso Dlamini, Sara R. Fedorka, Maisha S. Rashid, William R. Taylor, Veronika Kholodovych, Radhika Koranne, Mark W. Jackson, Tim Rogers, Ayad A. Al-Hamashi, Ibtissam Gad, Damian J. Junk, L. M. Viranga Tillekeratne, Nishanth Kuganesan, Yusuf Barudi, Hanan D. Alqahtani, Ronit Shah |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
lcsh:Medicine Antineoplastic Agents Article Mesoderm Small Molecule Libraries 03 medical and health sciences 0302 clinical medicine Breast cancer Cancer stem cell Neoplasms medicine Tumor Cells Cultured Ferroptosis Humans lcsh:Science Cell Proliferation Multidisciplinary biology Cell growth Mesenchymal stem cell lcsh:R medicine.disease Small molecule In vitro 3. Good health 030104 developmental biology Tubulin Apoptosis Cancer research biology.protein Neoplastic Stem Cells lcsh:Q Reactive Oxygen Species 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019) |
| ISSN: | 2045-2322 |
| Popis: | Effective management of advanced cancer requires systemic treatment including small molecules that target unique features of aggressive tumor cells. At the same time, tumors are heterogeneous and current evidence suggests that a subpopulation of tumor cells, called tumor initiating or cancer stem cells, are responsible for metastatic dissemination, tumor relapse and possibly drug resistance. Classical apoptotic drugs are less effective against this critical subpopulation. In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species to induce ferroptosis. Interestingly, we find that drug sensitivity is highest in tumor cells with a mesenchymal phenotype. Furthermore, these compounds showed enhanced toxicity towards mesenchymal breast cancer populations with cancer stem cell properties in vitro. In summary, we have identified a new class of small molecule ferroptotic agents that warrant further investigation. |
| Databáze: | OpenAIRE |
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