Novel platinum II and platinum IV complexes exhibit potent cytotoxicity and selectivity towards several cancer cell lines
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), breas...
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| Format: | masterThesis |
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2020
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| Online Access: | http://hdl.handle.net/10725/13850 https://doi.org/10.26756/th.2022.376 http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php |
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| _version_ | 1864513468322807808 |
|---|---|
| author | Elias, Elias |
| author_facet | Elias, Elias |
| author_role | author |
| dc.creator.none.fl_str_mv | Elias, Elias |
| dc.date.none.fl_str_mv | 2020 2020-05-14 2022-07-21T10:38:10Z 2022-07-21T10:38:10Z |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10725/13850 https://doi.org/10.26756/th.2022.376 http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php |
| dc.language.none.fl_str_mv | en |
| dc.publisher.none.fl_str_mv | Lebanese American University |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Platinum compounds -- Therapeutic use Cancer -- Chemotherapy Cell lines Lebanese American University -- Dissertations Dissertations, Academic |
| dc.title.none.fl_str_mv | Novel platinum II and platinum IV complexes exhibit potent cytotoxicity and selectivity towards several cancer cell lines |
| dc.type.none.fl_str_mv | Thesis info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/masterThesis |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | masterThesis |
| id | LAURepo_9f853b32d33f07d1b6dc4e66cda6fd34 |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/13850 |
| publishDate | 2020 |
| publisher.none.fl_str_mv | Lebanese American University |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Novel platinum II and platinum IV complexes exhibit potent cytotoxicity and selectivity towards several cancer cell linesElias, EliasPlatinum compounds -- Therapeutic useCancer -- ChemotherapyCell linesLebanese American University -- DissertationsDissertations, AcademicThe 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.1 online resource (xvi, 80 leaves): ill. (some col.)Includes bibliographical references (leaf 55-73).Lebanese American University2022-07-21T10:38:10Z2022-07-21T10:38:10Z20202020-05-14Thesisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttp://hdl.handle.net/10725/13850https://doi.org/10.26756/th.2022.376http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.phpeninfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/138502022-07-21T10:39:35Z |
| spellingShingle | Novel platinum II and platinum IV complexes exhibit potent cytotoxicity and selectivity towards several cancer cell lines Elias, Elias Platinum compounds -- Therapeutic use Cancer -- Chemotherapy Cell lines Lebanese American University -- Dissertations Dissertations, Academic |
| status_str | publishedVersion |
| title | Novel platinum II and platinum IV complexes exhibit potent cytotoxicity and selectivity towards several cancer cell lines |
| title_full | Novel platinum II and platinum IV complexes exhibit potent cytotoxicity and selectivity towards several cancer cell lines |
| title_fullStr | Novel platinum II and platinum IV complexes exhibit potent cytotoxicity and selectivity towards several cancer cell lines |
| title_full_unstemmed | Novel platinum II and platinum IV complexes exhibit potent cytotoxicity and selectivity towards several cancer cell lines |
| title_short | Novel platinum II and platinum IV complexes exhibit potent cytotoxicity and selectivity towards several cancer cell lines |
| title_sort | Novel platinum II and platinum IV complexes exhibit potent cytotoxicity and selectivity towards several cancer cell lines |
| topic | Platinum compounds -- Therapeutic use Cancer -- Chemotherapy Cell lines Lebanese American University -- Dissertations Dissertations, Academic |
| url | http://hdl.handle.net/10725/13850 https://doi.org/10.26756/th.2022.376 http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php |