Novel platinum (II) and platinum (IV) complexes exhibit potent chemotherapeutic properties in breast and skin cancer models

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dc.contributor.author Farah, Roudy
dc.date.accessioned 2022-10-26T06:50:11Z
dc.date.available 2022-10-26T06:50:11Z
dc.date.copyright 2022 en_US
dc.date.issued 2022-07-27
dc.identifier.uri http://hdl.handle.net/10725/14128
dc.description.abstract Following the discovery of cisplatin and its chemotherapeutic potential, many researchers started developing novel variations of platinum-based complexes to test their efficicacy in treating different types of cancer. The present study aims to determine the chemotherapeutic properties of a novel platinum (II) compound AK3 and its platinum (IV) analogue AK4 in the treatment of chemically-induced breast and skin cancer models. Cytotoxicity of complexes was first evaluated using WST-1 assay in MDA-MB-231 (breast) and A375 (skin) cancer cells 72 hours posttreatment. Cellular uptake was also determined by ICP-MS. The lethal and most tolerated doses were measured for both complexes in mice. The chemotherapeutic potential was assessed in a DMBA-induced breast cancer model in rats as well as a DMBA/TPA-induced skin cancer model in mice. The biodistribution of both complexes in mice was analyzed using ICP-MS. Both compounds showed higher cytotoxic activity than cisplatin and recorded IC50 values of 0.32 and 0.6 μM for AK3 and AK4 respectively against MDA-MB-231 cells, as well as 0.36 and 0.68 μM for AK3 and AK4 respectively against A375 cells. Both AK3 and AK4 were found to be mainly actively transported into MDA-MB-231 cells at significantly higher intracellular/extracellular concentrations ratios than cisplatin. Both complexes reported low toxicities in mice, especially the platinum (IV) compound AK4. In fact, the lethal and maximum tolerated doses were relatively high, recording 25-30 and > 20 mg/kg of body weight respectively in the case of AK3, as well as > 200 and > 50 mg/kg of body weight in the case of AK4. Both complexes exhibited remarkable chemotherapeutic potential in both breast and skin cancer models by greatly reducing tumor sizes up to 13-times in the breast cancer model as well as up to 6-times in the skin cancer model, compared to control groups. No significant change in organ or body weights was observed. Also, AK3 and AK4 were both readily available in the plasma, and AK3 was still available at high levels in the liver and kidneys 24h post-injection. In conclusion, both AK3 and AK4 could be considered as promising chemotherapeutic drugs in the treatment of both breast and skin cancer as well as potential alternatives for currently adopted platinum treatment regimens reporting severe side effects. en_US
dc.language.iso en en_US
dc.subject Platinum compounds -- Therapeutic use en_US
dc.subject Cancer -- Chemotherapy en_US
dc.subject Breast -- Cancer -- Molecular aspects en_US
dc.subject Skin -- Cancer -- Molecular aspects 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 chemotherapeutic properties in breast and skin cancer models en_US
dc.type Thesis en_US
dc.term.submitted Summer en_US
dc.author.degree Doctor of Pharmacy en_US
dc.author.school SAS en_US
dc.author.idnumber 201605455 en_US
dc.author.commembers Rizk-Jamati, Sandra
dc.author.commembers Khalaf, Roy
dc.author.department Natural Sciences en_US
dc.description.physdesc 1 online resource (xv, 68 leaves): ill. (some col.) en_US
dc.author.advisor Daher, Costantine
dc.keywords Platinum en_US
dc.keywords Cancer en_US
dc.keywords AK3 en_US
dc.keywords AK4 en_US
dc.keywords Cisplatin en_US
dc.keywords DMBA en_US
dc.keywords TPA en_US
dc.keywords Cytotoxicity en_US
dc.keywords Uptake en_US
dc.keywords Lethal Dose en_US
dc.keywords Most Tolerated Dose en_US
dc.keywords Chemotherapeutic Potential en_US
dc.keywords Biodistribution en_US
dc.description.bibliographiccitations Includes bibliographical references (leaves 59-68) en_US
dc.identifier.doi https://doi.org/10.26756/th.2022.456
dc.author.email roudy.farah@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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