A photoactivatable chemotherapeutic Ru(II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway
Photoactivated chemotherapy (PACT) is an emerging strategy for targeted cancer therapy. Strained Ru complexes with pseudo-octahedral geometry may undergo photo-induced ligand dissociation, forming aquated photoproducts that are significantly more cytotoxic compared to the precursor complex. The comp...
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| مؤلفون آخرون: | , , , |
| التنسيق: | article |
| منشور في: |
2021
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| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/14375 https://doi.org/10.1016/j.cbi.2021.109644 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.sciencedirect.com/science/article/pii/S0009279721002829 |
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| _version_ | 1864513469287497728 |
|---|---|
| author | Elias, Maria George |
| author2 | Mehanna, Stephanie Elias, Elias Khnayzer, Rony S. Daher, Costantine F. |
| author2_role | author author author author |
| author_facet | Elias, Maria George Mehanna, Stephanie Elias, Elias Khnayzer, Rony S. Daher, Costantine F. |
| author_role | author |
| dc.creator.none.fl_str_mv | Elias, Maria George Mehanna, Stephanie Elias, Elias Khnayzer, Rony S. Daher, Costantine F. |
| dc.date.none.fl_str_mv | 2021 2023-01-16T14:08:37Z 2023-01-16T14:08:37Z 2023-01-16 |
| dc.identifier.none.fl_str_mv | 0009-2797 http://hdl.handle.net/10725/14375 https://doi.org/10.1016/j.cbi.2021.109644 Elias, M. G., Mehanna, S., Elias, E., Khnayzer, R. S., & Daher, C. F. (2021). A photoactivatable chemotherapeutic Ru (II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway. Chemico-Biological Interactions, 348, 1-11. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.sciencedirect.com/science/article/pii/S0009279721002829 |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Chemico-Biological Interactions: A journal of molecular, cellular and biochemical toxicolog |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | A photoactivatable chemotherapeutic Ru(II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Photoactivated chemotherapy (PACT) is an emerging strategy for targeted cancer therapy. Strained Ru complexes with pseudo-octahedral geometry may undergo photo-induced ligand dissociation, forming aquated photoproducts that are significantly more cytotoxic compared to the precursor complex. The complexes investigated were the strained complex [Ru(bpy)2BC]Cl2 (where bpy = 2,2′-bipyridine and BC = bathocuproine) and its unstrained control [Ru(bpy)2phen]Cl2 (where phen = 1,10-phenanthroline). The uptake of [Ru(bpy)2BC]Cl2, assessed by ICP/MS, started immediately post-incubation and plateaued after 24 h. Active transport was found as the main mode of intracellular transport. Cell viability assays on A375 cells indicated a mean phototoxicity index of 340-fold, and the effect was shown to be primarily mediated by the aquated photoproducts rather than the dissociating ligands. A significant increase in ROS production and DNA damage was also observed. Flow cytometry confirmed the induction of early apoptosis at 48 h that proceeds to late apoptosis/necrosis by 72 h post-treatment. Western blot analysis of pro- and anti-apoptotic proteins revealed that apoptosis was mediated through an interplay between the intrinsic and extrinsic pathways, as well as autophagy and via inhibition of the MAPK and PI3K pathways. In conclusion, this study demonstrates that [Ru(bpy)2BC]Cl2 is a multi-mechanistic PACT drug which exhibits promising anticancer potential. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_3186e8a09cb64f8f6c716514067e0464 |
| identifier_str_mv | 0009-2797 Elias, M. G., Mehanna, S., Elias, E., Khnayzer, R. S., & Daher, C. F. (2021). A photoactivatable chemotherapeutic Ru (II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway. Chemico-Biological Interactions, 348, 1-11. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/14375 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | A photoactivatable chemotherapeutic Ru(II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathwayElias, Maria GeorgeMehanna, StephanieElias, EliasKhnayzer, Rony S.Daher, Costantine F.Photoactivated chemotherapy (PACT) is an emerging strategy for targeted cancer therapy. Strained Ru complexes with pseudo-octahedral geometry may undergo photo-induced ligand dissociation, forming aquated photoproducts that are significantly more cytotoxic compared to the precursor complex. The complexes investigated were the strained complex [Ru(bpy)2BC]Cl2 (where bpy = 2,2′-bipyridine and BC = bathocuproine) and its unstrained control [Ru(bpy)2phen]Cl2 (where phen = 1,10-phenanthroline). The uptake of [Ru(bpy)2BC]Cl2, assessed by ICP/MS, started immediately post-incubation and plateaued after 24 h. Active transport was found as the main mode of intracellular transport. Cell viability assays on A375 cells indicated a mean phototoxicity index of 340-fold, and the effect was shown to be primarily mediated by the aquated photoproducts rather than the dissociating ligands. A significant increase in ROS production and DNA damage was also observed. Flow cytometry confirmed the induction of early apoptosis at 48 h that proceeds to late apoptosis/necrosis by 72 h post-treatment. Western blot analysis of pro- and anti-apoptotic proteins revealed that apoptosis was mediated through an interplay between the intrinsic and extrinsic pathways, as well as autophagy and via inhibition of the MAPK and PI3K pathways. In conclusion, this study demonstrates that [Ru(bpy)2BC]Cl2 is a multi-mechanistic PACT drug which exhibits promising anticancer potential.Published2023-01-16T14:08:37Z2023-01-16T14:08:37Z20212023-01-16Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article0009-2797http://hdl.handle.net/10725/14375https://doi.org/10.1016/j.cbi.2021.109644Elias, M. G., Mehanna, S., Elias, E., Khnayzer, R. S., & Daher, C. F. (2021). A photoactivatable chemotherapeutic Ru (II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway. Chemico-Biological Interactions, 348, 1-11.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttps://www.sciencedirect.com/science/article/pii/S0009279721002829enChemico-Biological Interactions: A journal of molecular, cellular and biochemical toxicologinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/143752023-01-16T14:08:48Z |
| spellingShingle | A photoactivatable chemotherapeutic Ru(II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway Elias, Maria George |
| status_str | publishedVersion |
| title | A photoactivatable chemotherapeutic Ru(II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway |
| title_full | A photoactivatable chemotherapeutic Ru(II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway |
| title_fullStr | A photoactivatable chemotherapeutic Ru(II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway |
| title_full_unstemmed | A photoactivatable chemotherapeutic Ru(II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway |
| title_short | A photoactivatable chemotherapeutic Ru(II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway |
| title_sort | A photoactivatable chemotherapeutic Ru(II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway |
| url | http://hdl.handle.net/10725/14375 https://doi.org/10.1016/j.cbi.2021.109644 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.sciencedirect.com/science/article/pii/S0009279721002829 |