Publicação
Exploring the anticancer effect of new ruthenium-biotinylated conjugates in colorectal cancer
| Resumo: | Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a leading cause of cancer death worldwide. The current chemotherapeutic agents available for CRC treatment are limited, accompanied by severe side effects and resistance acquisition. Ruthenium (Ru) compounds have been explored because they encompass several anticancer properties that make them promising therapeutic agents. Considering this, two new ruthenium-biotinylated conjugates (LCR134 and LCR220) were recently synthesized, in an attempt to bring more efficiency and selectivity to target cancer cells. LCR134 comprises a Ru cytotoxic fragment, with the addition of two molecules of biotin to the organometallic center (active targeting), while LCR220 has a polymeric chain, with two biotin molecules at the end (passive and active targeting). The aim of this work was to determine whether these Ru-biotinylated conjugates are promising candidates for CRC therapy. In this work, the effects of the newly Ru agents were assessed in CRC cells (SW480 and RKO) and in a “normal” colon-derived cell line (NCM460). In order to achieve our aim, we studied the effect of Ru compounds on cell viability, cell death, F-actin cytoskeleton structure, as well as in β-actin and glucose transporters 1 (GLUT1) expression levels. The results showed that the compounds were more cytotoxic for CRC cell lines in comparison with the normal colon cells. Moreover, all the half-maximum inhibitory concentration (IC50) values with the exception of LCR134 for SW480 cells, were lower than the values of the classical chemotherapeutic agent cisplatin, suggesting a higher efficacy of our ruthenium-biotinylated conjugates towards CRC cells. Ru compounds also interfere with the clonogenic ability of both CRC cell lines, without inducing cell death in a significant manner, suggesting that their mechanism of action affects proliferation. Additionally, these agents induced structural changes in the cytoskeleton, namely in F-actin filaments. We could not observe alterations on the expression levels of β-actin and GLUT1. Our results highlight the promising anticancer activities of these agents towards CRC cells. |
|---|---|
| Autores principais: | Fernandes, Pedro José Pereira |
| Assunto: | Actin cytoskeleton Clonogenic ability Colorectal cancer Ruthenium Cancro colorretal Capacidade clonogénica Citoesqueleto de actina Ruténio |
| Ano: | 2020 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1866877211869446144 |
|---|---|
| author | Fernandes, Pedro José Pereira |
| author_facet | Fernandes, Pedro José Pereira |
| author_role | author |
| contributor_name_str_mv | Preto, Ana Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Fernandes, Pedro José Pereira\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Preto, Ana Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Fernandes, Pedro José Pereira |
| datacite.date.Accepted.fl_str_mv | 2020-01-28T00:00:00Z |
| datacite.date.available.fl_str_mv | 2022-11-08T12:00:07Z |
| datacite.date.embargoed.fl_str_mv | 2022-11-08T12:00:07Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Actin cytoskeleton Clonogenic ability Colorectal cancer Ruthenium Cancro colorretal Capacidade clonogénica Citoesqueleto de actina Ruténio |
| datacite.titles.title.fl_str_mv | Exploring the anticancer effect of new ruthenium-biotinylated conjugates in colorectal cancer Explorar o efeito anticancerígeno de novos conjugados de ruténio-biotinilados no cancro colorretal |
| dc.contributor.none.fl_str_mv | Preto, Ana Universidade do Minho |
| dc.creator.none.fl_str_mv | Fernandes, Pedro José Pereira |
| dc.date.Accepted.fl_str_mv | 2020-01-28T00:00:00Z |
| dc.date.available.fl_str_mv | 2022-11-08T12:00:07Z |
| dc.date.embargoed.fl_str_mv | 2022-11-08T12:00:07Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/80492 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.rights.rights.copyright.fl_str_mv | openAccess |
| dc.subject.none.fl_str_mv | Actin cytoskeleton Clonogenic ability Colorectal cancer Ruthenium Cancro colorretal Capacidade clonogénica Citoesqueleto de actina Ruténio |
| dc.title.fl_str_mv | Exploring the anticancer effect of new ruthenium-biotinylated conjugates in colorectal cancer Explorar o efeito anticancerígeno de novos conjugados de ruténio-biotinilados no cancro colorretal |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_bdcc |
| description | Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a leading cause of cancer death worldwide. The current chemotherapeutic agents available for CRC treatment are limited, accompanied by severe side effects and resistance acquisition. Ruthenium (Ru) compounds have been explored because they encompass several anticancer properties that make them promising therapeutic agents. Considering this, two new ruthenium-biotinylated conjugates (LCR134 and LCR220) were recently synthesized, in an attempt to bring more efficiency and selectivity to target cancer cells. LCR134 comprises a Ru cytotoxic fragment, with the addition of two molecules of biotin to the organometallic center (active targeting), while LCR220 has a polymeric chain, with two biotin molecules at the end (passive and active targeting). The aim of this work was to determine whether these Ru-biotinylated conjugates are promising candidates for CRC therapy. In this work, the effects of the newly Ru agents were assessed in CRC cells (SW480 and RKO) and in a “normal” colon-derived cell line (NCM460). In order to achieve our aim, we studied the effect of Ru compounds on cell viability, cell death, F-actin cytoskeleton structure, as well as in β-actin and glucose transporters 1 (GLUT1) expression levels. The results showed that the compounds were more cytotoxic for CRC cell lines in comparison with the normal colon cells. Moreover, all the half-maximum inhibitory concentration (IC50) values with the exception of LCR134 for SW480 cells, were lower than the values of the classical chemotherapeutic agent cisplatin, suggesting a higher efficacy of our ruthenium-biotinylated conjugates towards CRC cells. Ru compounds also interfere with the clonogenic ability of both CRC cell lines, without inducing cell death in a significant manner, suggesting that their mechanism of action affects proliferation. Additionally, these agents induced structural changes in the cytoskeleton, namely in F-actin filaments. We could not observe alterations on the expression levels of β-actin and GLUT1. Our results highlight the promising anticancer activities of these agents towards CRC cells. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | masterThesis |
| fulltext.url.fl_str_mv | https://prod-dspace.uminho.pt/bitstreams/ec8a547d-f6ca-4854-9144-7950016029fa/download |
| id | rum_eb5918dd7cd5ce8ea505d237b59ec30d |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/80492 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/80492 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Fernandes, Pedro José Pereira |
| publishDate | 2020 |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engporColorectal cancer (CRC) is one of the most commonly diagnosed cancers and a leading cause of cancer death worldwide. The current chemotherapeutic agents available for CRC treatment are limited, accompanied by severe side effects and resistance acquisition. Ruthenium (Ru) compounds have been explored because they encompass several anticancer properties that make them promising therapeutic agents. Considering this, two new ruthenium-biotinylated conjugates (LCR134 and LCR220) were recently synthesized, in an attempt to bring more efficiency and selectivity to target cancer cells. LCR134 comprises a Ru cytotoxic fragment, with the addition of two molecules of biotin to the organometallic center (active targeting), while LCR220 has a polymeric chain, with two biotin molecules at the end (passive and active targeting). The aim of this work was to determine whether these Ru-biotinylated conjugates are promising candidates for CRC therapy. In this work, the effects of the newly Ru agents were assessed in CRC cells (SW480 and RKO) and in a “normal” colon-derived cell line (NCM460). In order to achieve our aim, we studied the effect of Ru compounds on cell viability, cell death, F-actin cytoskeleton structure, as well as in β-actin and glucose transporters 1 (GLUT1) expression levels. The results showed that the compounds were more cytotoxic for CRC cell lines in comparison with the normal colon cells. Moreover, all the half-maximum inhibitory concentration (IC50) values with the exception of LCR134 for SW480 cells, were lower than the values of the classical chemotherapeutic agent cisplatin, suggesting a higher efficacy of our ruthenium-biotinylated conjugates towards CRC cells. Ru compounds also interfere with the clonogenic ability of both CRC cell lines, without inducing cell death in a significant manner, suggesting that their mechanism of action affects proliferation. Additionally, these agents induced structural changes in the cytoskeleton, namely in F-actin filaments. We could not observe alterations on the expression levels of β-actin and GLUT1. Our results highlight the promising anticancer activities of these agents towards CRC cells.application/pdfporExploring the anticancer effect of new ruthenium-biotinylated conjugates in colorectal cancerAlternativeTitleporExplorar o efeito anticancerígeno de novos conjugados de ruténio-biotinilados no cancro colorretalFernandes, Pedro José PereiraPreto, AnaHostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptURNurn:tid:2024741352022-11-08T12:00:07Z2020-01-282019-102020-01-28T00:00:00ZHandlehttps://hdl.handle.net/1822/80492http://purl.org/coar/access_right/c_abf2open accessActin cytoskeletonClonogenic abilityColorectal cancerRutheniumCancro colorretalCapacidade clonogénicaCitoesqueleto de actinaRuténio4114620 bytesliteraturehttp://purl.org/coar/resource_type/c_bdccmaster thesis2020-01-28http://creativecommons.org/licenses/by-nc-nd/4.0/openAccesshttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://prod-dspace.uminho.pt/bitstreams/ec8a547d-f6ca-4854-9144-7950016029fa/download |
| spellingShingle | Exploring the anticancer effect of new ruthenium-biotinylated conjugates in colorectal cancer Fernandes, Pedro José Pereira Actin cytoskeleton Clonogenic ability Colorectal cancer Ruthenium Cancro colorretal Capacidade clonogénica Citoesqueleto de actina Ruténio |
| status | SINGLETON |
| subject.fl_str_mv | Actin cytoskeleton Clonogenic ability Colorectal cancer Ruthenium Cancro colorretal Capacidade clonogénica Citoesqueleto de actina Ruténio |
| title | Exploring the anticancer effect of new ruthenium-biotinylated conjugates in colorectal cancer |
| title_full | Exploring the anticancer effect of new ruthenium-biotinylated conjugates in colorectal cancer |
| title_fullStr | Exploring the anticancer effect of new ruthenium-biotinylated conjugates in colorectal cancer |
| title_full_unstemmed | Exploring the anticancer effect of new ruthenium-biotinylated conjugates in colorectal cancer |
| title_short | Exploring the anticancer effect of new ruthenium-biotinylated conjugates in colorectal cancer |
| title_sort | Exploring the anticancer effect of new ruthenium-biotinylated conjugates in colorectal cancer |
| topic | Actin cytoskeleton Clonogenic ability Colorectal cancer Ruthenium Cancro colorretal Capacidade clonogénica Citoesqueleto de actina Ruténio |
| topic_facet | Actin cytoskeleton Clonogenic ability Colorectal cancer Ruthenium Cancro colorretal Capacidade clonogénica Citoesqueleto de actina Ruténio |
| url | https://hdl.handle.net/1822/80492 |
| visible | 1 |