Publicação
Assessment of a novel Cu (II) complex as a potential anticancer agent
| datacite.subject.fos | Engenharia e Tecnologia::Outras Engenharias e Tecnologias | pt_PT |
| dc.contributor.advisor | Fernandes, Maria Alexandra | |
| dc.contributor.advisor | Martins, Luísa | |
| dc.contributor.author | Santos, Sofia Guerreiro dos | |
| dc.date.accessioned | 2016-03-18T17:51:09Z | |
| dc.date.available | 2016-03-18T17:51:09Z | |
| dc.date.issued | 2015-09 | |
| dc.date.submitted | 2016-03 | |
| dc.description.abstract | Widely used in cancer treatment, chemotherapy still faces hindering challenges, ranging from severe induced toxicity to drug resistance acquisition. As means to overcome these setbacks, newly synthetized compounds have recently come into play with the basis of improved pharmacokinetic/pharmacodynamic properties. With this mind-set, this project aimed towards the antiproliferative potential characterization of a group of metallic compounds. Additionally the incorporation of the compounds within a nanoformulation and within new combination strategies with commercial chemotherapeutic drugs was also envisaged. Cell viability assays presented copper (II) compound (K4) as the most promising, presenting an IC50 of 6.10 μM and 19.09 μM for HCT116 and A549 cell line respectively. Exposure in fibroblasts revealed a 9.18 μM IC50. Hoechst staining assays further revealed the compound’s predisposition to induce chromatin condensation and nuclear fragmentation in HCT116 upon exposure to K4 which was later demonstrated by flow cytometry and annexin V-FITC/propidium iodide double staining analysis (under 50 % cell death induction). The compound further revealed the ability to interact with major macromolecules such as DNA (Kb = 2.17x105 M-1), inducing structural brakes and retardation, and further affecting cell cycle progression revealing delay in S-phase. Moreover BSA interactions were also visible however not conclusive. Proteome profiling revealed overexpression of proteins involved in metabolic activity and underexpression of proteins involved in apoptosis thus corroborating Hoechst and apoptosis flow cytometry data. K4 nanoformulation suffered from several hindrances and was ill succeeded in part due to K4’s poor solubility in aqueous buffers. Other approaches were considered in this regard. Combined chemotherapy assays revealed high cytotoxicity for afatinib and lapatinib strategies. Lapatinib and K4 proteome profiling further revealed high apoptosis rates, high metabolic activity and activation of redundant proteins as part of compensatory mechanisms. | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10362/16845 | |
| dc.language.iso | eng | pt_PT |
| dc.subject | Cancer | pt_PT |
| dc.subject | Chemotherapy | pt_PT |
| dc.subject | Colorectal cancer | pt_PT |
| dc.subject | Copper compounds | pt_PT |
| dc.subject | Combined therapy | pt_PT |
| dc.subject | Nanovectorization | pt_PT |
| dc.title | Assessment of a novel Cu (II) complex as a potential anticancer agent | pt_PT |
| dc.type | master thesis | |
| dspace.entity.type | Publication | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | masterThesis | pt_PT |
| thesis.degree.name | Mestrado em Genética Molecular e Biomedicina | pt_PT |