001     305791
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024 7 _ |a 10.1038/s41388-018-0654-9
|2 doi
024 7 _ |a pmid:30622338
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024 7 _ |a 0950-9232
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024 7 _ |a 1476-5594
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037 _ _ |a DKFZ-2025-02408
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Gold, Ayala
|b 0
245 _ _ |a Spironolactone inhibits the growth of cancer stem cells by impairing DNA damage response.
260 _ _ |a London
|c 2019
|b Springer Nature
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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500 _ _ |a #DKFZ-MOST-Ca180#
520 _ _ |a The cancer stem cell (CSC) model suggests that a subpopulation of cells within the tumor, the CSCs, is responsible for cancer relapse and metastasis formation. CSCs hold unique characteristics, such as self-renewal, differentiation abilities, and resistance to chemotherapy, raising the need for discovering drugs that target CSCs. Previously we have found that the antihypertensive drug spironolactone impairs DNA damage response in cancer cells. Here we show that spironolactone, apart from inhibiting cancerous cell growth, is also highly toxic to CSCs. Notably, we demonstrate that CSCs have high basal levels of DNA double-strand breaks (DSBs). Mechanistically, we reveal that spironolactone does not damage the DNA but impairs DSB repair and induces apoptosis in cancer cells and CSCs while sparing healthy cells. In vivo, spironolactone treatment reduced the size and CSC content of tumors. Overall, we suggest spironolactone as an anticancer reagent, toxic to both cancer cells and, particularly to, CSCs.
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
650 _ 7 |a Antineoplastic Agents
|2 NLM Chemicals
650 _ 7 |a Spironolactone
|0 27O7W4T232
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Antineoplastic Agents: administration & dosage
|2 MeSH
650 _ 2 |a Antineoplastic Agents: pharmacology
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Cell Proliferation
|2 MeSH
650 _ 2 |a Cell Survival: drug effects
|2 MeSH
650 _ 2 |a DNA Repair: drug effects
|2 MeSH
650 _ 2 |a Drug Repositioning
|2 MeSH
650 _ 2 |a HeLa Cells
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Neoplasms: drug therapy
|2 MeSH
650 _ 2 |a Neoplasms: genetics
|2 MeSH
650 _ 2 |a Neoplastic Stem Cells: drug effects
|2 MeSH
650 _ 2 |a Spironolactone: administration & dosage
|2 MeSH
650 _ 2 |a Spironolactone: pharmacology
|2 MeSH
650 _ 2 |a Xenograft Model Antitumor Assays
|2 MeSH
700 1 _ |a Eini, Lital
|b 1
700 1 _ |a Nissim-Rafinia, Malka
|b 2
700 1 _ |a Viner, Ruth
|b 3
700 1 _ |a Ezer, Shlomit
|b 4
700 1 _ |a Erez, Keren
|b 5
700 1 _ |a Aqaqe, Nasma
|b 6
700 1 _ |a Hanania, Rotem
|b 7
700 1 _ |a Milyavsky, Michael
|0 0000-0002-5083-0809
|b 8
700 1 _ |a Meshorer, Eran
|b 9
700 1 _ |a Goldberg, Michal
|b 10
773 _ _ |a 10.1038/s41388-018-0654-9
|g Vol. 38, no. 17, p. 3103 - 3118
|0 PERI:(DE-600)2008404-3
|n 17
|p 3103 - 3118
|t Oncogene
|v 38
|y 2019
|x 0950-9232
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