The mechanistic role of cardiac glycosides in DNA damage response and repair signaling

dc.contributor.authorAinembabazi, Diana
dc.contributor.authorZhang, Youwei
dc.contributor.authorTurchi, John J.
dc.contributor.departmentMedicine, School of Medicine
dc.date.accessioned2024-02-21T20:39:48Z
dc.date.available2024-02-21T20:39:48Z
dc.date.issued2023-08-16
dc.description.abstractCardiac glycosides (CGs) are a class of bioactive organic compounds well-known for their application in treating heart disease despite a narrow therapeutic window. Considerable evidence has demonstrated the potential to repurpose CGs for cancer treatment. Chemical modification of these CGs has been utilized in attempts to increase their anti-cancer properties; however, this has met limited success as their mechanism of action is still speculative. Recent studies have identified the DNA damage response (DDR) pathway as a target of CGs. DDR serves to coordinate numerous cellular pathways to initiate cell cycle arrest, promote DNA repair, regulate replication fork firing and protection, or induce apoptosis to avoid the survival of cells with DNA damage or cells carrying mutations. Understanding the modus operandi of cardiac glycosides will provide critical information to better address improvements in potency, reduced toxicity, and the potential to overcome drug resistance. This review summarizes recent scientific findings of the molecular mechanisms of cardiac glycosides affecting the DDR signaling pathway in cancer therapeutics from 2010 to 2022. We focus on the structural and functional differences of CGs toward identifying the critical features for DDR targeting of these agents.
dc.eprint.versionFinal published version
dc.identifier.citationAinembabazi D, Zhang Y, Turchi JJ. The mechanistic role of cardiac glycosides in DNA damage response and repair signaling. Cell Mol Life Sci. 2023;80(9):250. Published 2023 Aug 16. doi:10.1007/s00018-023-04910-9
dc.identifier.urihttps://hdl.handle.net/1805/38585
dc.language.isoen_US
dc.publisherSpringer
dc.relation.isversionof10.1007/s00018-023-04910-9
dc.relation.journalCellular and Molecular Life Sciences
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.sourcePMC
dc.subjectCardenolide
dc.subjectBufadienolide
dc.subjectCancer therapeutics
dc.subjectCytotoxicity
dc.subjectStructure–activity relationships
dc.titleThe mechanistic role of cardiac glycosides in DNA damage response and repair signaling
dc.typeArticle
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
18_2023_Article_4910.pdf
Size:
1.33 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.99 KB
Format:
Item-specific license agreed upon to submission
Description: