Unveiling the Chemotherapeutic Potential of Novel Platinum II and Platinum IV Complexes in Skin and Breast Cancers: In Vitro and In Vivo Insights
Thesis (M.S.) -- Biological Sciences, May 2024
محفوظ في:
| المؤلف الرئيسي: | |
|---|---|
| التنسيق: | masterThesis |
| منشور في: |
2024
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| الموضوعات: | |
| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/15978 https://doi.org/10.26756/th.2023.686 http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php |
| الوسوم: |
إضافة وسم
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| _version_ | 1864513471824003072 |
|---|---|
| author | Slika, Amjad |
| author_facet | Slika, Amjad |
| author_role | author |
| dc.creator.none.fl_str_mv | Slika, Amjad |
| dc.date.none.fl_str_mv | 2024-08-14T07:51:19Z 2024-08-14T07:51:19Z 2024 2024-05-14 |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10725/15978 https://doi.org/10.26756/th.2023.686 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 | Breast -- Cancer -- Molecular aspects Skin -- Cancer -- Molecular aspects Platinum compounds -- Therapeutic use Cancer -- Chemotherapy Lebanese American University -- Dissertations Dissertations, Academic |
| dc.title.none.fl_str_mv | Unveiling the Chemotherapeutic Potential of Novel Platinum II and Platinum IV Complexes in Skin and Breast Cancers: In Vitro and In Vivo Insights |
| dc.type.none.fl_str_mv | Thesis info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/masterThesis |
| description | Thesis (M.S.) -- Biological Sciences, May 2024 |
| eu_rights_str_mv | openAccess |
| format | masterThesis |
| id | LAURepo_b0ca2a35083cab8ec0d697e8949b5ff7 |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/15978 |
| publishDate | 2024 |
| publisher.none.fl_str_mv | Lebanese American University |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Unveiling the Chemotherapeutic Potential of Novel Platinum II and Platinum IV Complexes in Skin and Breast Cancers: In Vitro and In Vivo InsightsSlika, AmjadBreast -- Cancer -- Molecular aspectsSkin -- Cancer -- Molecular aspectsPlatinum compounds -- Therapeutic useCancer -- ChemotherapyLebanese American University -- DissertationsDissertations, AcademicThesis (M.S.) -- Biological Sciences, May 2024Includes bibliographical references (leaves 97-115)Platinum-based drugs, like cisplatin, have been extensively utilized in cancer chemotherapy. However, their clinical application is limited due to the development of off target toxicity and drug resistance. Despite these obstacles, chemotherapy is the most common and effective way of killing cancer cells. Thus, novel platinum(II) and platinum(IV) based complexes with modified ligands have recently been considered as potential candidates to overcome the therapeutic side-effects, bringing the prospect for effective and safe therapy. In this study, we will analyze and establish the chemotherapeutic efficacy and toxicity of the novel platinum(II) complex 5ClSS(II), its platinum(IV) analogue 5ClSS(IV), and two novel platinum(IV) compounds, P-PENT and P-HEX. The research utilizes a comprehensive approach that combines the use of in vitro and in vivo techniques to test the anticancer and safety profile of these complexes on skin and breast cancer. Cytotoxic activity of the complexes has been shown on HaCaT and MDA-MB-231 cell lines with IC50 values in the low micromolar range. The IC50 of P-PENT and P-HEX was found to be approximately ten times lower towards mesenchymal stem cells compared to cancer cells, demonstrating their improved targeting efficiency. All complexes caused apoptosis, release of reactive oxygen species, and simulated key apoptosis and survival pathways such as Bcl-2, Bax, caspase-3, cytochrome c, Akt, and ERK. In vivo chemotherapeutic efficacy and safety of the complexes were also tested on DMBA/TPA-induced skin carcinogenesis model in mice and DMBA-induced breast carcinogenesis model in rats. The two models showed dose-responsive action with respect to inhibition of tumor growth. This anticancer effect was manifested at drug concentrations well below the maximum tolerated dose, and without significant adverse effects. Body and organs weights, and kidney and liver functions were not affected throughout the treatment process, indicating a safe profile. This work highlights the chemotherapeutic potential and safety of these novel complexes which make them candidates for further development towards clinical evaluation. Additional research is needed to understand their mechanism of action and uncover other molecular targets to maximize their clinical use in cancer treatment.1 online resource (xv, 116 leaves) : col. ill.Lebanese American University2024-08-14T07:51:19Z2024-08-14T07:51:19Z20242024-05-14Thesisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttp://hdl.handle.net/10725/15978https://doi.org/10.26756/th.2023.686http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.phpeninfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/159782024-12-11T06:44:50Z |
| spellingShingle | Unveiling the Chemotherapeutic Potential of Novel Platinum II and Platinum IV Complexes in Skin and Breast Cancers: In Vitro and In Vivo Insights Slika, Amjad Breast -- Cancer -- Molecular aspects Skin -- Cancer -- Molecular aspects Platinum compounds -- Therapeutic use Cancer -- Chemotherapy Lebanese American University -- Dissertations Dissertations, Academic |
| status_str | publishedVersion |
| title | Unveiling the Chemotherapeutic Potential of Novel Platinum II and Platinum IV Complexes in Skin and Breast Cancers: In Vitro and In Vivo Insights |
| title_full | Unveiling the Chemotherapeutic Potential of Novel Platinum II and Platinum IV Complexes in Skin and Breast Cancers: In Vitro and In Vivo Insights |
| title_fullStr | Unveiling the Chemotherapeutic Potential of Novel Platinum II and Platinum IV Complexes in Skin and Breast Cancers: In Vitro and In Vivo Insights |
| title_full_unstemmed | Unveiling the Chemotherapeutic Potential of Novel Platinum II and Platinum IV Complexes in Skin and Breast Cancers: In Vitro and In Vivo Insights |
| title_short | Unveiling the Chemotherapeutic Potential of Novel Platinum II and Platinum IV Complexes in Skin and Breast Cancers: In Vitro and In Vivo Insights |
| title_sort | Unveiling the Chemotherapeutic Potential of Novel Platinum II and Platinum IV Complexes in Skin and Breast Cancers: In Vitro and In Vivo Insights |
| topic | Breast -- Cancer -- Molecular aspects Skin -- Cancer -- Molecular aspects Platinum compounds -- Therapeutic use Cancer -- Chemotherapy Lebanese American University -- Dissertations Dissertations, Academic |
| url | http://hdl.handle.net/10725/15978 https://doi.org/10.26756/th.2023.686 http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php |