Novel platinum II and platinum IV complexes exhibit potent cytotoxicity and selectivity towards several cancer cell lines

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dc.contributor.author Elias, Elias
dc.date.accessioned 2022-07-21T10:38:10Z
dc.date.available 2022-07-21T10:38:10Z
dc.date.copyright 2020 en_US
dc.date.issued 2020-05-14
dc.identifier.uri http://hdl.handle.net/10725/13850
dc.description.abstract The discovery of cisplatin and its antineoplastic potential directed research toward the usage of platinum-based complexes as chemotherapeutical drugs. The aim of the present study is to test the anticancer activity of two novel platinum complexes Pt(II) and Pt(IV) on lung cancer cells (A549), breast cancer cells (MDA-MB-231), melanoma cells (A375), and mesenchymal stem cells (MSC), and evaluate the mechanism of action involved. Cell viability was assessed 72 hours post-treatment using MTS assay. The cellular uptake of both compounds was measured by ICP-MS. Their effect on DNA fragmentation was then tested using Comet assay. The type of cell death was assessed by flow cytometry. Evaluation of apoptotic proteins’ expression was performed using western blots. Results showed that both complexes significantly reduced cancer cell viability and exhibited 7 to 20-fold higher cytotoxicity compared to cisplatin. Pt(IV) showed remarkable selectivity towards different cancer cells (17-22 fold) compared with mesenchymal stem cells. While both complexes were actively transported into the cells, Pt(II) showed a faster and higher uptake compared to its platinum IV analogue. Pt(IV) but not Pt(II) treatment caused significant DNA fragmentation in A549 cells. Western blot analysis demonstrated an upregulation of Bax/Bcl-2 ratio and cytochrome c, downregulation of procaspases 3 and 9 and cleavage of Parp for both Pt(II) and Pt(IV), which indicates that apoptosis was induced through the intrinsic pathway. No effect on procaspase 8 was observed, eliminating the involvement of the extrinsic apoptotic pathway. Flow cytometry analysis confirmed the apoptotic cell death caused by both platinum complexes. In conclusion, Pt(II) and Pt(IV) may be considered as promising anti-cancer drugs with Pt(IV) being more selective to cancer cells, which might provide a robust alternative for currently approved anticancer platinum medications. en_US
dc.language.iso en en_US
dc.subject Platinum compounds -- Therapeutic use en_US
dc.subject Cancer -- Chemotherapy en_US
dc.subject Cell lines en_US
dc.subject Lebanese American University -- Dissertations en_US
dc.subject Dissertations, Academic en_US
dc.title Novel platinum II and platinum IV complexes exhibit potent cytotoxicity and selectivity towards several cancer cell lines en_US
dc.type Thesis en_US
dc.term.submitted Spring en_US
dc.author.degree MS in Molecular Biology en_US
dc.author.school SAS en_US
dc.author.idnumber 201401805 en_US
dc.author.commembers Khalaf, Roy
dc.author.commembers Khalil, Christian
dc.author.department N/A en_US
dc.description.physdesc 1 online resource (xvi, 80 leaves): ill. (some col.) en_US
dc.author.advisor Khnayzer, Rony
dc.author.advisor Taleb, Robin
dc.keywords Platinum en_US
dc.keywords Cancer en_US
dc.keywords Pt(II) en_US
dc.keywords Pt(IV) en_US
dc.keywords Cisplatin en_US
dc.keywords Cytotoxicity en_US
dc.keywords Selectivity en_US
dc.keywords DNA Fragmentation en_US
dc.keywords Intrinsic en_US
dc.keywords Apoptosis en_US
dc.description.bibliographiccitations Includes bibliographical references (leaf 55-73). en_US
dc.identifier.doi https://doi.org/10.26756/th.2022.376
dc.author.email elias.elias01@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php en_US
dc.publisher.institution Lebanese American University en_US
dc.author.affiliation Lebanese American University en_US

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